diff --git a/content/2.defense-systems/abia.md b/content/2.defense-systems/abia.md index a212c32688031cb335dc4ff5660b6293f7542693..330be5b1f1034d23d6e43489c83ab7af88ec98b2 100644 --- a/content/2.defense-systems/abia.md +++ b/content/2.defense-systems/abia.md @@ -32,12 +32,12 @@ A system from \*lactococcal plasmid\* in \*lactococci\* has an anti-phage effect ## Relevant abstracts -\*\*Chopin, M.-C., Chopin, A. & Bidnenko, E. Phage abortive infection in lactococci: variations on a theme. Curr Opin Microbiol 8, 473-479 (2005).\*\* -Abortive infection (Abi) systems, also called phage exclusion, block phage multiplication and cause premature bacterial cell death upon phage infection. This decreases the number of progeny particles and limits their spread to other cells allowing the bacterial population to survive. Twenty Abi systems have been isolated in Lactococcus lactis, a bacterium used in cheese-making fermentation processes, where phage attacks are of economical importance. Recent insights in their expression and mode of action indicate that, behind diverse phenotypic and molecular effects, lactococcal Abis share common traits with the well-studied Escherichia coli systems Lit and Prr. Abis are widespread in bacteria, and recent analysis indicates that Abis might have additional roles other than conferring phage resistance. - -\*\*Forde, A. & Fitzgerald, G. F. Bacteriophage defence systems in lactic acid bacteria. Antonie Van Leeuwenhoek 76, 89-113 (1999).\*\* -The study of the interactions between lactic acid bacteria and their bacteriophages has been a vibrant and rewarding research activity for a considerable number of years. In the more recent past, the application of molecular genetics for the analysis of phage-host relationships has contributed enormously to the unravelling of specific events which dictate insensitivity to bacteriophage infection and has revealed that while they are complex and intricate in nature, they are also extremely effective. In addition, the strategy has laid solid foundations for the construction of phage resistant strains for use in commercial applications and has provided a sound basis for continued investigations into existing, naturally-derived and novel, genetically-engineered defence systems. Of course, it has also become clear that phage particles are highly dynamic in their response to those defence systems which they do encounter and that they can readily adapt to them as a consequence of their genetic flexibility and plasticity. This paper reviews the exciting developments that have been described in the literature regarding the study of phage-host interactions in lactic acid bacteria and the innovative approaches that can be taken to exploit this basic information for curtailing phage infection. - -\*\*Mestre, M. R. et al. UG/Abi: a highly diverse family of prokaryotic reverse transcriptases associated with defense functions. Nucleic Acids Research 50, 6084-6101 (2022).\*\* -Reverse transcriptases (RTs) are enzymes capable of synthesizing DNA using RNA as a template. Within the last few years, a burst of research has led to the discovery of novel prokaryotic RTs with diverse antiviral properties, such as DRTs (Defense-associated RTs), which belong to the so-called group of unknown RTs (UG) and are closely related to the Abortive Infection system (Abi) RTs. In this work, we performed a systematic analysis of UG and Abi RTs, increasing the number of UG/Abi members up to 42 highly diverse groups, most of which are predicted to be functionally associated with other gene(s) or domain(s). Based on this information, we classified these systems into three major classes. In addition, we reveal that most of these groups are associated with defense functions and/or mobile genetic elements, and demonstrate the antiphage role of four novel groups. Besides, we highlight the presence of one of these systems in novel families of human gut viruses infecting members of the Bacteroidetes and Firmicutes phyla. This work lays the foundation for a comprehensive and unified understanding of these highly diverse RTs with enormous biotechnological potential. +::article-doi-list +--- +items: + - 10.1023/A:1002027321171 + - 10.1016/j.mib.2005.06.006 + - 10.1093/nar/gkac467 +--- +:: diff --git a/content/2.defense-systems/abib.md b/content/2.defense-systems/abib.md index a21572970e50cdac463a807fffe0f12fc5b11dec..bc399c55c8f13eb0e3d0d50c360a84c5c1856eab 100644 --- a/content/2.defense-systems/abib.md +++ b/content/2.defense-systems/abib.md @@ -28,9 +28,11 @@ A system from \*lactococcal plasmid\* in \*lactococci\* has an anti-phage effect ## Relevant abstracts -\*\*Chopin, M.-C., Chopin, A. & Bidnenko, E. Phage abortive infection in lactococci: variations on a theme. Curr Opin Microbiol 8, 473-479 (2005).\*\* -Abortive infection (Abi) systems, also called phage exclusion, block phage multiplication and cause premature bacterial cell death upon phage infection. This decreases the number of progeny particles and limits their spread to other cells allowing the bacterial population to survive. Twenty Abi systems have been isolated in Lactococcus lactis, a bacterium used in cheese-making fermentation processes, where phage attacks are of economical importance. Recent insights in their expression and mode of action indicate that, behind diverse phenotypic and molecular effects, lactococcal Abis share common traits with the well-studied Escherichia coli systems Lit and Prr. Abis are widespread in bacteria, and recent analysis indicates that Abis might have additional roles other than conferring phage resistance. - -\*\*Forde, A. & Fitzgerald, G. F. Bacteriophage defence systems in lactic acid bacteria. Antonie Van Leeuwenhoek 76, 89-113 (1999).\*\* -The study of the interactions between lactic acid bacteria and their bacteriophages has been a vibrant and rewarding research activity for a considerable number of years. In the more recent past, the application of molecular genetics for the analysis of phage-host relationships has contributed enormously to the unravelling of specific events which dictate insensitivity to bacteriophage infection and has revealed that while they are complex and intricate in nature, they are also extremely effective. In addition, the strategy has laid solid foundations for the construction of phage resistant strains for use in commercial applications and has provided a sound basis for continued investigations into existing, naturally-derived and novel, genetically-engineered defence systems. Of course, it has also become clear that phage particles are highly dynamic in their response to those defence systems which they do encounter and that they can readily adapt to them as a consequence of their genetic flexibility and plasticity. This paper reviews the exciting developments that have been described in the literature regarding the study of phage-host interactions in lactic acid bacteria and the innovative approaches that can be taken to exploit this basic information for curtailing phage infection. +::article-doi-list +--- +items: + - 10.1023/A:1002027321171 + - 10.1016/j.mib.2005.06.006 +--- +:: diff --git a/content/2.defense-systems/abic.md b/content/2.defense-systems/abic.md index 67b6d4939dacd066b11c9cdf00130e7df3e80b48..8cf4a7dc50166881e4ee6e56c32d41326470be69 100644 --- a/content/2.defense-systems/abic.md +++ b/content/2.defense-systems/abic.md @@ -34,9 +34,11 @@ A system from \*lactococcal plasmid\* in \*lactococci\* has an anti-phage effect ## Relevant abstracts -\*\*Chopin, M.-C., Chopin, A. & Bidnenko, E. Phage abortive infection in lactococci: variations on a theme. Curr Opin Microbiol 8, 473-479 (2005).\*\* -Abortive infection (Abi) systems, also called phage exclusion, block phage multiplication and cause premature bacterial cell death upon phage infection. This decreases the number of progeny particles and limits their spread to other cells allowing the bacterial population to survive. Twenty Abi systems have been isolated in Lactococcus lactis, a bacterium used in cheese-making fermentation processes, where phage attacks are of economical importance. Recent insights in their expression and mode of action indicate that, behind diverse phenotypic and molecular effects, lactococcal Abis share common traits with the well-studied Escherichia coli systems Lit and Prr. Abis are widespread in bacteria, and recent analysis indicates that Abis might have additional roles other than conferring phage resistance. - -\*\*Forde, A. & Fitzgerald, G. F. Bacteriophage defence systems in lactic acid bacteria. Antonie Van Leeuwenhoek 76, 89-113 (1999).\*\* -The study of the interactions between lactic acid bacteria and their bacteriophages has been a vibrant and rewarding research activity for a considerable number of years. In the more recent past, the application of molecular genetics for the analysis of phage-host relationships has contributed enormously to the unravelling of specific events which dictate insensitivity to bacteriophage infection and has revealed that while they are complex and intricate in nature, they are also extremely effective. In addition, the strategy has laid solid foundations for the construction of phage resistant strains for use in commercial applications and has provided a sound basis for continued investigations into existing, naturally-derived and novel, genetically-engineered defence systems. Of course, it has also become clear that phage particles are highly dynamic in their response to those defence systems which they do encounter and that they can readily adapt to them as a consequence of their genetic flexibility and plasticity. This paper reviews the exciting developments that have been described in the literature regarding the study of phage-host interactions in lactic acid bacteria and the innovative approaches that can be taken to exploit this basic information for curtailing phage infection. +::article-doi-list +--- +items: + - 10.1023/A:1002027321171 + - 10.1016/j.mib.2005.06.006 +--- +:: diff --git a/content/2.defense-systems/abid.md b/content/2.defense-systems/abid.md index b883f7c516190ce7eb0379a152f58dd8601deb48..94d81ae8ea31c6c74de5d0aacb2cd3cbc7d04518 100644 --- a/content/2.defense-systems/abid.md +++ b/content/2.defense-systems/abid.md @@ -28,9 +28,11 @@ A system from \*lactococcal plasmid\* in \*lactococci\* has an anti-phage effect ## Relevant abstracts -\*\*Chopin, M.-C., Chopin, A. & Bidnenko, E. Phage abortive infection in lactococci: variations on a theme. Curr Opin Microbiol 8, 473-479 (2005).\*\* -Abortive infection (Abi) systems, also called phage exclusion, block phage multiplication and cause premature bacterial cell death upon phage infection. This decreases the number of progeny particles and limits their spread to other cells allowing the bacterial population to survive. Twenty Abi systems have been isolated in Lactococcus lactis, a bacterium used in cheese-making fermentation processes, where phage attacks are of economical importance. Recent insights in their expression and mode of action indicate that, behind diverse phenotypic and molecular effects, lactococcal Abis share common traits with the well-studied Escherichia coli systems Lit and Prr. Abis are widespread in bacteria, and recent analysis indicates that Abis might have additional roles other than conferring phage resistance. - -\*\*Forde, A. & Fitzgerald, G. F. Bacteriophage defence systems in lactic acid bacteria. Antonie Van Leeuwenhoek 76, 89-113 (1999).\*\* -The study of the interactions between lactic acid bacteria and their bacteriophages has been a vibrant and rewarding research activity for a considerable number of years. In the more recent past, the application of molecular genetics for the analysis of phage-host relationships has contributed enormously to the unravelling of specific events which dictate insensitivity to bacteriophage infection and has revealed that while they are complex and intricate in nature, they are also extremely effective. In addition, the strategy has laid solid foundations for the construction of phage resistant strains for use in commercial applications and has provided a sound basis for continued investigations into existing, naturally-derived and novel, genetically-engineered defence systems. Of course, it has also become clear that phage particles are highly dynamic in their response to those defence systems which they do encounter and that they can readily adapt to them as a consequence of their genetic flexibility and plasticity. This paper reviews the exciting developments that have been described in the literature regarding the study of phage-host interactions in lactic acid bacteria and the innovative approaches that can be taken to exploit this basic information for curtailing phage infection. +::article-doi-list +--- +items: + - 10.1023/A:1002027321171 + - 10.1016/j.mib.2005.06.006 +--- +:: diff --git a/content/2.defense-systems/abie.md b/content/2.defense-systems/abie.md index ce2f4bca0fb55e6b9385458a9ca27fa3dccbb60a..0828199265b948ec176b387c71667f59a56a6581 100644 --- a/content/2.defense-systems/abie.md +++ b/content/2.defense-systems/abie.md @@ -40,12 +40,12 @@ A system from \*lactococcal plasmid\* in \*lactococci\* has an anti-phage effect ## Relevant abstracts -\*\*Chopin, M.-C., Chopin, A. & Bidnenko, E. Phage abortive infection in lactococci: variations on a theme. Curr Opin Microbiol 8, 473-479 (2005).\*\* -Abortive infection (Abi) systems, also called phage exclusion, block phage multiplication and cause premature bacterial cell death upon phage infection. This decreases the number of progeny particles and limits their spread to other cells allowing the bacterial population to survive. Twenty Abi systems have been isolated in Lactococcus lactis, a bacterium used in cheese-making fermentation processes, where phage attacks are of economical importance. Recent insights in their expression and mode of action indicate that, behind diverse phenotypic and molecular effects, lactococcal Abis share common traits with the well-studied Escherichia coli systems Lit and Prr. Abis are widespread in bacteria, and recent analysis indicates that Abis might have additional roles other than conferring phage resistance. - -\*\*Dy, R. L., Przybilski, R., Semeijn, K., Salmond, G. P. C. & Fineran, P. C. A widespread bacteriophage abortive infection system functions through a Type IV toxin-antitoxin mechanism. Nucleic Acids Res 42, 4590-4605 (2014).\*\* -Bacterial abortive infection (Abi) systems are 'altruistic' cell death systems that are activated by phage infection and limit viral replication, thereby providing protection to the bacterial population. Here, we have used a novel approach of screening Abi systems as a tool to identify and characterize toxin-antitoxin (TA)-acting Abi systems. We show that AbiE systems are encoded by bicistronic operons and function via a non-interacting (Type IV) bacteriostatic TA mechanism. The abiE operon was negatively autoregulated by the antitoxin, AbiEi, a member of a widespread family of putative transcriptional regulators. AbiEi has an N-terminal winged-helix-turn-helix domain that is required for repression of abiE transcription, and an uncharacterized bi-functional C-terminal domain, which is necessary for transcriptional repression and sufficient for toxin neutralization. The cognate toxin, AbiEii, is a predicted nucleotidyltransferase (NTase) and member of the DNA polymerase ? family. AbiEii specifically bound GTP, and mutations in conserved NTase motifs (I-III) and a newly identified motif (IV), abolished GTP binding and subsequent toxicity. The AbiE systems can provide phage resistance and enable stabilization of mobile genetic elements, such as plasmids. Our study reveals molecular insights into the regulation and function of the widespread bi-functional AbiE Abi-TA systems and the biochemical properties of both toxin and antitoxin proteins. - -\*\*Forde, A. & Fitzgerald, G. F. Bacteriophage defence systems in lactic acid bacteria. Antonie Van Leeuwenhoek 76, 89-113 (1999).\*\* -The study of the interactions between lactic acid bacteria and their bacteriophages has been a vibrant and rewarding research activity for a considerable number of years. In the more recent past, the application of molecular genetics for the analysis of phage-host relationships has contributed enormously to the unravelling of specific events which dictate insensitivity to bacteriophage infection and has revealed that while they are complex and intricate in nature, they are also extremely effective. In addition, the strategy has laid solid foundations for the construction of phage resistant strains for use in commercial applications and has provided a sound basis for continued investigations into existing, naturally-derived and novel, genetically-engineered defence systems. Of course, it has also become clear that phage particles are highly dynamic in their response to those defence systems which they do encounter and that they can readily adapt to them as a consequence of their genetic flexibility and plasticity. This paper reviews the exciting developments that have been described in the literature regarding the study of phage-host interactions in lactic acid bacteria and the innovative approaches that can be taken to exploit this basic information for curtailing phage infection. +::article-doi-list +--- +items: + - 10.1023/A:1002027321171 + - 10.1016/j.mib.2005.06.006 + - 10.1093/nar/gkt1419 +--- +:: diff --git a/content/2.defense-systems/abig.md b/content/2.defense-systems/abig.md index 1b3b780bb4a8b37ae17c58144cdbfc23242cc302..6212ea72d108c786cb61c01b89ef75c58db7c868 100644 --- a/content/2.defense-systems/abig.md +++ b/content/2.defense-systems/abig.md @@ -28,9 +28,11 @@ A system from \*lactococcal plasmid\* in \*lactococci\* has an anti-phage effect ## Relevant abstracts -\*\*Chopin, M.-C., Chopin, A. & Bidnenko, E. Phage abortive infection in lactococci: variations on a theme. Curr Opin Microbiol 8, 473-479 (2005).\*\* -Abortive infection (Abi) systems, also called phage exclusion, block phage multiplication and cause premature bacterial cell death upon phage infection. This decreases the number of progeny particles and limits their spread to other cells allowing the bacterial population to survive. Twenty Abi systems have been isolated in Lactococcus lactis, a bacterium used in cheese-making fermentation processes, where phage attacks are of economical importance. Recent insights in their expression and mode of action indicate that, behind diverse phenotypic and molecular effects, lactococcal Abis share common traits with the well-studied Escherichia coli systems Lit and Prr. Abis are widespread in bacteria, and recent analysis indicates that Abis might have additional roles other than conferring phage resistance. - -\*\*Forde, A. & Fitzgerald, G. F. Bacteriophage defence systems in lactic acid bacteria. Antonie Van Leeuwenhoek 76, 89-113 (1999).\*\* -The study of the interactions between lactic acid bacteria and their bacteriophages has been a vibrant and rewarding research activity for a considerable number of years. In the more recent past, the application of molecular genetics for the analysis of phage-host relationships has contributed enormously to the unravelling of specific events which dictate insensitivity to bacteriophage infection and has revealed that while they are complex and intricate in nature, they are also extremely effective. In addition, the strategy has laid solid foundations for the construction of phage resistant strains for use in commercial applications and has provided a sound basis for continued investigations into existing, naturally-derived and novel, genetically-engineered defence systems. Of course, it has also become clear that phage particles are highly dynamic in their response to those defence systems which they do encounter and that they can readily adapt to them as a consequence of their genetic flexibility and plasticity. This paper reviews the exciting developments that have been described in the literature regarding the study of phage-host interactions in lactic acid bacteria and the innovative approaches that can be taken to exploit this basic information for curtailing phage infection. +::article-doi-list +--- +items: + - 10.1023/A:1002027321171 + - 10.1016/j.mib.2005.06.006 +--- +:: diff --git a/content/2.defense-systems/abih.md b/content/2.defense-systems/abih.md index 185e7e7a5e2141d41d46c808c592f4fb51895236..390f36ef0ffaabd6870a33f7b7c75032ec8f9598 100644 --- a/content/2.defense-systems/abih.md +++ b/content/2.defense-systems/abih.md @@ -30,12 +30,12 @@ A system from \*lactococci\* in \*lactococci\* has an anti-phage effect against ## Relevant abstracts -\*\*Chopin, M.-C., Chopin, A. & Bidnenko, E. Phage abortive infection in lactococci: variations on a theme. Curr Opin Microbiol 8, 473-479 (2005).\*\* -Abortive infection (Abi) systems, also called phage exclusion, block phage multiplication and cause premature bacterial cell death upon phage infection. This decreases the number of progeny particles and limits their spread to other cells allowing the bacterial population to survive. Twenty Abi systems have been isolated in Lactococcus lactis, a bacterium used in cheese-making fermentation processes, where phage attacks are of economical importance. Recent insights in their expression and mode of action indicate that, behind diverse phenotypic and molecular effects, lactococcal Abis share common traits with the well-studied Escherichia coli systems Lit and Prr. Abis are widespread in bacteria, and recent analysis indicates that Abis might have additional roles other than conferring phage resistance. - -\*\*Forde, A. & Fitzgerald, G. F. Bacteriophage defence systems in lactic acid bacteria. Antonie Van Leeuwenhoek 76, 89-113 (1999).\*\* -The study of the interactions between lactic acid bacteria and their bacteriophages has been a vibrant and rewarding research activity for a considerable number of years. In the more recent past, the application of molecular genetics for the analysis of phage-host relationships has contributed enormously to the unravelling of specific events which dictate insensitivity to bacteriophage infection and has revealed that while they are complex and intricate in nature, they are also extremely effective. In addition, the strategy has laid solid foundations for the construction of phage resistant strains for use in commercial applications and has provided a sound basis for continued investigations into existing, naturally-derived and novel, genetically-engineered defence systems. Of course, it has also become clear that phage particles are highly dynamic in their response to those defence systems which they do encounter and that they can readily adapt to them as a consequence of their genetic flexibility and plasticity. This paper reviews the exciting developments that have been described in the literature regarding the study of phage-host interactions in lactic acid bacteria and the innovative approaches that can be taken to exploit this basic information for curtailing phage infection. - -\*\*Prévots, F., Daloyau, M., Bonin, O., Dumont, X. & Tolou, S. Cloning and sequencing of the novel abortive infection gene abiH of Lactococcus lactis ssp. lactis biovar. diacetylactis S94. FEMS Microbiol Lett 142, 295-299 (1996).\*\* -A gene which encodes resistance by abortive infection (Abi+) to bacteriophage was cloned from Lactococcus lactis ssp. lactis biovar. diacetylactis S94. This gene was found to confer a reduction in efficiency of plating and plaque size for prolate-headed bacteriophage phi 53 (group I of homology) and total resistance to the small isometric-headed bacteriophage phi 59 (group III of homology). The cloned gene is predicted to encode a polypeptide of 346 amino acid residues with a deduced molecular mass of 41 455 Da. No homology with any previously described genes was found. A probe was used to determine the presence of this gene in two strains on 31 tested. +::article-doi-list +--- +items: + - 10.1023/A:1002027321171 + - 10.1016/j.mib.2005.06.006 + - 10.1111/j.1574-6968.1996.tb08446.x +--- +:: diff --git a/content/2.defense-systems/abii.md b/content/2.defense-systems/abii.md index 05ce92068ed2a149a66d4b614f4163d4dbdcb676..74dccabcb5d901bc8f8ca7105c2ff3e957671dc8 100644 --- a/content/2.defense-systems/abii.md +++ b/content/2.defense-systems/abii.md @@ -30,9 +30,11 @@ A system from \*lactococcal plasmid\* in \*lactococci\* has an anti-phage effect ## Relevant abstracts -\*\*Chopin, M.-C., Chopin, A. & Bidnenko, E. Phage abortive infection in lactococci: variations on a theme. Curr Opin Microbiol 8, 473-479 (2005).\*\* -Abortive infection (Abi) systems, also called phage exclusion, block phage multiplication and cause premature bacterial cell death upon phage infection. This decreases the number of progeny particles and limits their spread to other cells allowing the bacterial population to survive. Twenty Abi systems have been isolated in Lactococcus lactis, a bacterium used in cheese-making fermentation processes, where phage attacks are of economical importance. Recent insights in their expression and mode of action indicate that, behind diverse phenotypic and molecular effects, lactococcal Abis share common traits with the well-studied Escherichia coli systems Lit and Prr. Abis are widespread in bacteria, and recent analysis indicates that Abis might have additional roles other than conferring phage resistance. - -\*\*Forde, A. & Fitzgerald, G. F. Bacteriophage defence systems in lactic acid bacteria. Antonie Van Leeuwenhoek 76, 89-113 (1999).\*\* -The study of the interactions between lactic acid bacteria and their bacteriophages has been a vibrant and rewarding research activity for a considerable number of years. In the more recent past, the application of molecular genetics for the analysis of phage-host relationships has contributed enormously to the unravelling of specific events which dictate insensitivity to bacteriophage infection and has revealed that while they are complex and intricate in nature, they are also extremely effective. In addition, the strategy has laid solid foundations for the construction of phage resistant strains for use in commercial applications and has provided a sound basis for continued investigations into existing, naturally-derived and novel, genetically-engineered defence systems. Of course, it has also become clear that phage particles are highly dynamic in their response to those defence systems which they do encounter and that they can readily adapt to them as a consequence of their genetic flexibility and plasticity. This paper reviews the exciting developments that have been described in the literature regarding the study of phage-host interactions in lactic acid bacteria and the innovative approaches that can be taken to exploit this basic information for curtailing phage infection. +::article-doi-list +--- +items: + - 10.1023/A:1002027321171 + - 10.1016/j.mib.2005.06.006 +--- +:: diff --git a/content/2.defense-systems/abij.md b/content/2.defense-systems/abij.md index 198f32cc1519c121822b8a2dacf1cc561dc7f957..e11da1a31c16b17ff287b3e9a5e8c2766d35e5cd 100644 --- a/content/2.defense-systems/abij.md +++ b/content/2.defense-systems/abij.md @@ -30,9 +30,11 @@ A system from \*lactococcal plasmid\* in \*lactococci\* has an anti-phage effect ## Relevant abstracts -\*\*Chopin, M.-C., Chopin, A. & Bidnenko, E. Phage abortive infection in lactococci: variations on a theme. Curr Opin Microbiol 8, 473-479 (2005).\*\* -Abortive infection (Abi) systems, also called phage exclusion, block phage multiplication and cause premature bacterial cell death upon phage infection. This decreases the number of progeny particles and limits their spread to other cells allowing the bacterial population to survive. Twenty Abi systems have been isolated in Lactococcus lactis, a bacterium used in cheese-making fermentation processes, where phage attacks are of economical importance. Recent insights in their expression and mode of action indicate that, behind diverse phenotypic and molecular effects, lactococcal Abis share common traits with the well-studied Escherichia coli systems Lit and Prr. Abis are widespread in bacteria, and recent analysis indicates that Abis might have additional roles other than conferring phage resistance. - -\*\*Forde, A. & Fitzgerald, G. F. Bacteriophage defence systems in lactic acid bacteria. Antonie Van Leeuwenhoek 76, 89-113 (1999).\*\* -The study of the interactions between lactic acid bacteria and their bacteriophages has been a vibrant and rewarding research activity for a considerable number of years. In the more recent past, the application of molecular genetics for the analysis of phage-host relationships has contributed enormously to the unravelling of specific events which dictate insensitivity to bacteriophage infection and has revealed that while they are complex and intricate in nature, they are also extremely effective. In addition, the strategy has laid solid foundations for the construction of phage resistant strains for use in commercial applications and has provided a sound basis for continued investigations into existing, naturally-derived and novel, genetically-engineered defence systems. Of course, it has also become clear that phage particles are highly dynamic in their response to those defence systems which they do encounter and that they can readily adapt to them as a consequence of their genetic flexibility and plasticity. This paper reviews the exciting developments that have been described in the literature regarding the study of phage-host interactions in lactic acid bacteria and the innovative approaches that can be taken to exploit this basic information for curtailing phage infection. +::article-doi-list +--- +items: + - 10.1023/A:1002027321171 + - 10.1016/j.mib.2005.06.006 +--- +:: diff --git a/content/2.defense-systems/abik.md b/content/2.defense-systems/abik.md index 839f449bcc7b103dc3fa78d5f2b17dc44fcc6315..e54df0e1d208ae582cdd78e52c258d5b506ceac4 100644 --- a/content/2.defense-systems/abik.md +++ b/content/2.defense-systems/abik.md @@ -30,12 +30,12 @@ A system from \*lactococcal plasmid\* in \*lactococci\* has an anti-phage effect ## Relevant abstracts -\*\*Chopin, M.-C., Chopin, A. & Bidnenko, E. Phage abortive infection in lactococci: variations on a theme. Curr Opin Microbiol 8, 473-479 (2005).\*\* -Abortive infection (Abi) systems, also called phage exclusion, block phage multiplication and cause premature bacterial cell death upon phage infection. This decreases the number of progeny particles and limits their spread to other cells allowing the bacterial population to survive. Twenty Abi systems have been isolated in Lactococcus lactis, a bacterium used in cheese-making fermentation processes, where phage attacks are of economical importance. Recent insights in their expression and mode of action indicate that, behind diverse phenotypic and molecular effects, lactococcal Abis share common traits with the well-studied Escherichia coli systems Lit and Prr. Abis are widespread in bacteria, and recent analysis indicates that Abis might have additional roles other than conferring phage resistance. - -\*\*Forde, A. & Fitzgerald, G. F. Bacteriophage defence systems in lactic acid bacteria. Antonie Van Leeuwenhoek 76, 89-113 (1999).\*\* -The study of the interactions between lactic acid bacteria and their bacteriophages has been a vibrant and rewarding research activity for a considerable number of years. In the more recent past, the application of molecular genetics for the analysis of phage-host relationships has contributed enormously to the unravelling of specific events which dictate insensitivity to bacteriophage infection and has revealed that while they are complex and intricate in nature, they are also extremely effective. In addition, the strategy has laid solid foundations for the construction of phage resistant strains for use in commercial applications and has provided a sound basis for continued investigations into existing, naturally-derived and novel, genetically-engineered defence systems. Of course, it has also become clear that phage particles are highly dynamic in their response to those defence systems which they do encounter and that they can readily adapt to them as a consequence of their genetic flexibility and plasticity. This paper reviews the exciting developments that have been described in the literature regarding the study of phage-host interactions in lactic acid bacteria and the innovative approaches that can be taken to exploit this basic information for curtailing phage infection. - -\*\*Mestre, M. R. et al. UG/Abi: a highly diverse family of prokaryotic reverse transcriptases associated with defense functions. Nucleic Acids Research 50, 6084-6101 (2022).\*\* -Reverse transcriptases (RTs) are enzymes capable of synthesizing DNA using RNA as a template. Within the last few years, a burst of research has led to the discovery of novel prokaryotic RTs with diverse antiviral properties, such as DRTs (Defense-associated RTs), which belong to the so-called group of unknown RTs (UG) and are closely related to the Abortive Infection system (Abi) RTs. In this work, we performed a systematic analysis of UG and Abi RTs, increasing the number of UG/Abi members up to 42 highly diverse groups, most of which are predicted to be functionally associated with other gene(s) or domain(s). Based on this information, we classified these systems into three major classes. In addition, we reveal that most of these groups are associated with defense functions and/or mobile genetic elements, and demonstrate the antiphage role of four novel groups. Besides, we highlight the presence of one of these systems in novel families of human gut viruses infecting members of the Bacteroidetes and Firmicutes phyla. This work lays the foundation for a comprehensive and unified understanding of these highly diverse RTs with enormous biotechnological potential. +::article-doi-list +--- +items: + - 10.1023/A:1002027321171 + - 10.1016/j.mib.2005.06.006 + - 10.1093/nar/gkac467 +--- +:: diff --git a/content/2.defense-systems/abil.md b/content/2.defense-systems/abil.md index 983f8780500789561208e144149f5562a626f794..48bc2166b9f58456e3f5446158dd9d73218030eb 100644 --- a/content/2.defense-systems/abil.md +++ b/content/2.defense-systems/abil.md @@ -30,9 +30,11 @@ A system from \*lactococcal plasmid\* in \*lactococci\* has an anti-phage effect ## Relevant abstracts -\*\*Chopin, M.-C., Chopin, A. & Bidnenko, E. Phage abortive infection in lactococci: variations on a theme. Curr Opin Microbiol 8, 473-479 (2005).\*\* -Abortive infection (Abi) systems, also called phage exclusion, block phage multiplication and cause premature bacterial cell death upon phage infection. This decreases the number of progeny particles and limits their spread to other cells allowing the bacterial population to survive. Twenty Abi systems have been isolated in Lactococcus lactis, a bacterium used in cheese-making fermentation processes, where phage attacks are of economical importance. Recent insights in their expression and mode of action indicate that, behind diverse phenotypic and molecular effects, lactococcal Abis share common traits with the well-studied Escherichia coli systems Lit and Prr. Abis are widespread in bacteria, and recent analysis indicates that Abis might have additional roles other than conferring phage resistance. - -\*\*Forde, A. & Fitzgerald, G. F. Bacteriophage defence systems in lactic acid bacteria. Antonie Van Leeuwenhoek 76, 89-113 (1999).\*\* -The study of the interactions between lactic acid bacteria and their bacteriophages has been a vibrant and rewarding research activity for a considerable number of years. In the more recent past, the application of molecular genetics for the analysis of phage-host relationships has contributed enormously to the unravelling of specific events which dictate insensitivity to bacteriophage infection and has revealed that while they are complex and intricate in nature, they are also extremely effective. In addition, the strategy has laid solid foundations for the construction of phage resistant strains for use in commercial applications and has provided a sound basis for continued investigations into existing, naturally-derived and novel, genetically-engineered defence systems. Of course, it has also become clear that phage particles are highly dynamic in their response to those defence systems which they do encounter and that they can readily adapt to them as a consequence of their genetic flexibility and plasticity. This paper reviews the exciting developments that have been described in the literature regarding the study of phage-host interactions in lactic acid bacteria and the innovative approaches that can be taken to exploit this basic information for curtailing phage infection. +::article-doi-list +--- +items: + - 10.1023/A:1002027321171 + - 10.1016/j.mib.2005.06.006 +--- +:: diff --git a/content/2.defense-systems/abin.md b/content/2.defense-systems/abin.md index 1931a637a1cf808929e37b73e725552c7e2288bd..ea2c042b42d10b23b834b8c1e0870d9c593e4598 100644 --- a/content/2.defense-systems/abin.md +++ b/content/2.defense-systems/abin.md @@ -30,9 +30,11 @@ A system from \*lactococcal prophage\* in \*lactococci\* has an anti-phage effec ## Relevant abstracts -\*\*Chopin, M.-C., Chopin, A. & Bidnenko, E. Phage abortive infection in lactococci: variations on a theme. Curr Opin Microbiol 8, 473-479 (2005).\*\* -Abortive infection (Abi) systems, also called phage exclusion, block phage multiplication and cause premature bacterial cell death upon phage infection. This decreases the number of progeny particles and limits their spread to other cells allowing the bacterial population to survive. Twenty Abi systems have been isolated in Lactococcus lactis, a bacterium used in cheese-making fermentation processes, where phage attacks are of economical importance. Recent insights in their expression and mode of action indicate that, behind diverse phenotypic and molecular effects, lactococcal Abis share common traits with the well-studied Escherichia coli systems Lit and Prr. Abis are widespread in bacteria, and recent analysis indicates that Abis might have additional roles other than conferring phage resistance. - -\*\*Forde, A. & Fitzgerald, G. F. Bacteriophage defence systems in lactic acid bacteria. Antonie Van Leeuwenhoek 76, 89-113 (1999).\*\* -The study of the interactions between lactic acid bacteria and their bacteriophages has been a vibrant and rewarding research activity for a considerable number of years. In the more recent past, the application of molecular genetics for the analysis of phage-host relationships has contributed enormously to the unravelling of specific events which dictate insensitivity to bacteriophage infection and has revealed that while they are complex and intricate in nature, they are also extremely effective. In addition, the strategy has laid solid foundations for the construction of phage resistant strains for use in commercial applications and has provided a sound basis for continued investigations into existing, naturally-derived and novel, genetically-engineered defence systems. Of course, it has also become clear that phage particles are highly dynamic in their response to those defence systems which they do encounter and that they can readily adapt to them as a consequence of their genetic flexibility and plasticity. This paper reviews the exciting developments that have been described in the literature regarding the study of phage-host interactions in lactic acid bacteria and the innovative approaches that can be taken to exploit this basic information for curtailing phage infection. +::article-doi-list +--- +items: + - 10.1023/A:1002027321171 + - 10.1016/j.mib.2005.06.006 +--- +:: diff --git a/content/2.defense-systems/abio.md b/content/2.defense-systems/abio.md index 66224af798a39cb1deb8eea541b9983924c0ef9e..377fb61ea744d18ca2eb2e1e6c49d11cce42875b 100644 --- a/content/2.defense-systems/abio.md +++ b/content/2.defense-systems/abio.md @@ -30,9 +30,11 @@ A system from \*lactococcal plasmid\* in \*lactococci\* has an anti-phage effect ## Relevant abstracts -\*\*Chopin, M.-C., Chopin, A. & Bidnenko, E. Phage abortive infection in lactococci: variations on a theme. Curr Opin Microbiol 8, 473-479 (2005).\*\* -Abortive infection (Abi) systems, also called phage exclusion, block phage multiplication and cause premature bacterial cell death upon phage infection. This decreases the number of progeny particles and limits their spread to other cells allowing the bacterial population to survive. Twenty Abi systems have been isolated in Lactococcus lactis, a bacterium used in cheese-making fermentation processes, where phage attacks are of economical importance. Recent insights in their expression and mode of action indicate that, behind diverse phenotypic and molecular effects, lactococcal Abis share common traits with the well-studied Escherichia coli systems Lit and Prr. Abis are widespread in bacteria, and recent analysis indicates that Abis might have additional roles other than conferring phage resistance. - -\*\*Forde, A. & Fitzgerald, G. F. Bacteriophage defence systems in lactic acid bacteria. Antonie Van Leeuwenhoek 76, 89-113 (1999).\*\* -The study of the interactions between lactic acid bacteria and their bacteriophages has been a vibrant and rewarding research activity for a considerable number of years. In the more recent past, the application of molecular genetics for the analysis of phage-host relationships has contributed enormously to the unravelling of specific events which dictate insensitivity to bacteriophage infection and has revealed that while they are complex and intricate in nature, they are also extremely effective. In addition, the strategy has laid solid foundations for the construction of phage resistant strains for use in commercial applications and has provided a sound basis for continued investigations into existing, naturally-derived and novel, genetically-engineered defence systems. Of course, it has also become clear that phage particles are highly dynamic in their response to those defence systems which they do encounter and that they can readily adapt to them as a consequence of their genetic flexibility and plasticity. This paper reviews the exciting developments that have been described in the literature regarding the study of phage-host interactions in lactic acid bacteria and the innovative approaches that can be taken to exploit this basic information for curtailing phage infection. +::article-doi-list +--- +items: + - 10.1023/A:1002027321171 + - 10.1016/j.mib.2005.06.006 +--- +:: diff --git a/content/2.defense-systems/abip2.md b/content/2.defense-systems/abip2.md index 6dff3b8b9a2754678246a22ecb6d0d707e6daaa5..c51303e970f387cb428287eedbc5ca4fe0f2299d 100644 --- a/content/2.defense-systems/abip2.md +++ b/content/2.defense-systems/abip2.md @@ -32,12 +32,12 @@ A system from \*lactococcal plasmid\* in \*lactococci\* has an anti-phage effect ## Relevant abstracts -\*\*Chopin, M.-C., Chopin, A. & Bidnenko, E. Phage abortive infection in lactococci: variations on a theme. Curr Opin Microbiol 8, 473-479 (2005).\*\* -Abortive infection (Abi) systems, also called phage exclusion, block phage multiplication and cause premature bacterial cell death upon phage infection. This decreases the number of progeny particles and limits their spread to other cells allowing the bacterial population to survive. Twenty Abi systems have been isolated in Lactococcus lactis, a bacterium used in cheese-making fermentation processes, where phage attacks are of economical importance. Recent insights in their expression and mode of action indicate that, behind diverse phenotypic and molecular effects, lactococcal Abis share common traits with the well-studied Escherichia coli systems Lit and Prr. Abis are widespread in bacteria, and recent analysis indicates that Abis might have additional roles other than conferring phage resistance. - -\*\*Forde, A. & Fitzgerald, G. F. Bacteriophage defence systems in lactic acid bacteria. Antonie Van Leeuwenhoek 76, 89-113 (1999).\*\* -The study of the interactions between lactic acid bacteria and their bacteriophages has been a vibrant and rewarding research activity for a considerable number of years. In the more recent past, the application of molecular genetics for the analysis of phage-host relationships has contributed enormously to the unravelling of specific events which dictate insensitivity to bacteriophage infection and has revealed that while they are complex and intricate in nature, they are also extremely effective. In addition, the strategy has laid solid foundations for the construction of phage resistant strains for use in commercial applications and has provided a sound basis for continued investigations into existing, naturally-derived and novel, genetically-engineered defence systems. Of course, it has also become clear that phage particles are highly dynamic in their response to those defence systems which they do encounter and that they can readily adapt to them as a consequence of their genetic flexibility and plasticity. This paper reviews the exciting developments that have been described in the literature regarding the study of phage-host interactions in lactic acid bacteria and the innovative approaches that can be taken to exploit this basic information for curtailing phage infection. - -\*\*Mestre, M. R. et al. UG/Abi: a highly diverse family of prokaryotic reverse transcriptases associated with defense functions. Nucleic Acids Research 50, 6084-6101 (2022).\*\* -Reverse transcriptases (RTs) are enzymes capable of synthesizing DNA using RNA as a template. Within the last few years, a burst of research has led to the discovery of novel prokaryotic RTs with diverse antiviral properties, such as DRTs (Defense-associated RTs), which belong to the so-called group of unknown RTs (UG) and are closely related to the Abortive Infection system (Abi) RTs. In this work, we performed a systematic analysis of UG and Abi RTs, increasing the number of UG/Abi members up to 42 highly diverse groups, most of which are predicted to be functionally associated with other gene(s) or domain(s). Based on this information, we classified these systems into three major classes. In addition, we reveal that most of these groups are associated with defense functions and/or mobile genetic elements, and demonstrate the antiphage role of four novel groups. Besides, we highlight the presence of one of these systems in novel families of human gut viruses infecting members of the Bacteroidetes and Firmicutes phyla. This work lays the foundation for a comprehensive and unified understanding of these highly diverse RTs with enormous biotechnological potential. +::article-doi-list +--- +items: + - 10.1023/A:1002027321171 + - 10.1016/j.mib.2005.06.006 + - 10.1093/nar/gkac467 +--- +:: diff --git a/content/2.defense-systems/abiq.md b/content/2.defense-systems/abiq.md index aea83f8263663a6744dde0ae922206e13a491836..14cd8c8c9a44c917d0941d97ebb6f2d0d298fe33 100644 --- a/content/2.defense-systems/abiq.md +++ b/content/2.defense-systems/abiq.md @@ -30,12 +30,12 @@ A system from \*lactococcal plasmid\* in \*lactococci\* has an anti-phage effect ## Relevant abstracts -\*\*Chopin, M.-C., Chopin, A. & Bidnenko, E. Phage abortive infection in lactococci: variations on a theme. Curr Opin Microbiol 8, 473-479 (2005).\*\* -Abortive infection (Abi) systems, also called phage exclusion, block phage multiplication and cause premature bacterial cell death upon phage infection. This decreases the number of progeny particles and limits their spread to other cells allowing the bacterial population to survive. Twenty Abi systems have been isolated in Lactococcus lactis, a bacterium used in cheese-making fermentation processes, where phage attacks are of economical importance. Recent insights in their expression and mode of action indicate that, behind diverse phenotypic and molecular effects, lactococcal Abis share common traits with the well-studied Escherichia coli systems Lit and Prr. Abis are widespread in bacteria, and recent analysis indicates that Abis might have additional roles other than conferring phage resistance. - -\*\*Emond, E. et al. AbiQ, an abortive infection mechanism from Lactococcus lactis. Appl Environ Microbiol 64, 4748-4756 (1998).\*\* -Lactococcus lactis W-37 is highly resistant to phage infection. The cryptic plasmids from this strain were coelectroporated, along with the shuttle vector pSA3, into the plasmid-free host L. lactis LM0230. In addition to pSA3, erythromycin- and phage-resistant isolates carried pSRQ900, an 11-kb plasmid from L. lactis W-37. This plasmid made the host bacteria highly resistant (efficiency of plaquing <10(-8)) to c2- and 936-like phages. pSRQ900 did not confer any resistance to phages of the P335 species. Adsorption, cell survival, and endonucleolytic activity assays showed that pSRQ900 encodes an abortive infection mechanism. The phage resistance mechanism is limited to a 2.2-kb EcoRV/BclI fragment. Sequence analysis of this fragment revealed a complete open reading frame (abiQ), which encodes a putative protein of 183 amino acids. A frameshift mutation within abiQ completely abolished the resistant phenotype. The predicted peptide has a high content of positively charged residues (pI = 10.5) and is, in all likelihood, a cytosolic protein. AbiQ has no homology to known or deduced proteins in the databases. DNA replication assays showed that phage c21 (c2-like) and phage p2 (936-like) can still replicate in cells harboring AbiQ. However, phage DNA accumulated in its concatenated form in the infected AbiQ+ cells, whereas the AbiQ- cells contained processed (mature) phage DNA in addition to the concatenated form. The production of the major capsid protein of phage c21 was not hindered in the cells harboring AbiQ. - -\*\*Forde, A. & Fitzgerald, G. F. Bacteriophage defence systems in lactic acid bacteria. Antonie Van Leeuwenhoek 76, 89-113 (1999).\*\* -The study of the interactions between lactic acid bacteria and their bacteriophages has been a vibrant and rewarding research activity for a considerable number of years. In the more recent past, the application of molecular genetics for the analysis of phage-host relationships has contributed enormously to the unravelling of specific events which dictate insensitivity to bacteriophage infection and has revealed that while they are complex and intricate in nature, they are also extremely effective. In addition, the strategy has laid solid foundations for the construction of phage resistant strains for use in commercial applications and has provided a sound basis for continued investigations into existing, naturally-derived and novel, genetically-engineered defence systems. Of course, it has also become clear that phage particles are highly dynamic in their response to those defence systems which they do encounter and that they can readily adapt to them as a consequence of their genetic flexibility and plasticity. This paper reviews the exciting developments that have been described in the literature regarding the study of phage-host interactions in lactic acid bacteria and the innovative approaches that can be taken to exploit this basic information for curtailing phage infection. +::article-doi-list +--- +items: + - 10.1023/A:1002027321171 + - 10.1016/j.mib.2005.06.006 + - 10.1128/AEM.64.12.4748-4756.1998 +--- +:: diff --git a/content/2.defense-systems/abir.md b/content/2.defense-systems/abir.md index ffc6c775f304802c702d30aefc0ddff9211a0d6b..03fbabddd300a0b657e7a8be2e0bf52073a0da4c 100644 --- a/content/2.defense-systems/abir.md +++ b/content/2.defense-systems/abir.md @@ -30,9 +30,11 @@ A system from \*lactococcal plasmid\* in \*lactococci\* has an anti-phage effect ## Relevant abstracts -\*\*Chopin, M.-C., Chopin, A. & Bidnenko, E. Phage abortive infection in lactococci: variations on a theme. Curr Opin Microbiol 8, 473-479 (2005).\*\* -Abortive infection (Abi) systems, also called phage exclusion, block phage multiplication and cause premature bacterial cell death upon phage infection. This decreases the number of progeny particles and limits their spread to other cells allowing the bacterial population to survive. Twenty Abi systems have been isolated in Lactococcus lactis, a bacterium used in cheese-making fermentation processes, where phage attacks are of economical importance. Recent insights in their expression and mode of action indicate that, behind diverse phenotypic and molecular effects, lactococcal Abis share common traits with the well-studied Escherichia coli systems Lit and Prr. Abis are widespread in bacteria, and recent analysis indicates that Abis might have additional roles other than conferring phage resistance. - -\*\*Forde, A. & Fitzgerald, G. F. Bacteriophage defence systems in lactic acid bacteria. Antonie Van Leeuwenhoek 76, 89-113 (1999).\*\* -The study of the interactions between lactic acid bacteria and their bacteriophages has been a vibrant and rewarding research activity for a considerable number of years. In the more recent past, the application of molecular genetics for the analysis of phage-host relationships has contributed enormously to the unravelling of specific events which dictate insensitivity to bacteriophage infection and has revealed that while they are complex and intricate in nature, they are also extremely effective. In addition, the strategy has laid solid foundations for the construction of phage resistant strains for use in commercial applications and has provided a sound basis for continued investigations into existing, naturally-derived and novel, genetically-engineered defence systems. Of course, it has also become clear that phage particles are highly dynamic in their response to those defence systems which they do encounter and that they can readily adapt to them as a consequence of their genetic flexibility and plasticity. This paper reviews the exciting developments that have been described in the literature regarding the study of phage-host interactions in lactic acid bacteria and the innovative approaches that can be taken to exploit this basic information for curtailing phage infection. +::article-doi-list +--- +items: + - 10.1023/A:1002027321171 + - 10.1016/j.mib.2005.06.006 +--- +:: diff --git a/content/2.defense-systems/abit.md b/content/2.defense-systems/abit.md index 6ce67e66251881eb241dd054f05fabd741d24f84..54cedcc907534d59c4350f1e4cd75dd352c72889 100644 --- a/content/2.defense-systems/abit.md +++ b/content/2.defense-systems/abit.md @@ -30,9 +30,11 @@ A system from \*lactococcal plasmid\* in \*lactococci\* has an anti-phage effect ## Relevant abstracts -\*\*Chopin, M.-C., Chopin, A. & Bidnenko, E. Phage abortive infection in lactococci: variations on a theme. Curr Opin Microbiol 8, 473-479 (2005).\*\* -Abortive infection (Abi) systems, also called phage exclusion, block phage multiplication and cause premature bacterial cell death upon phage infection. This decreases the number of progeny particles and limits their spread to other cells allowing the bacterial population to survive. Twenty Abi systems have been isolated in Lactococcus lactis, a bacterium used in cheese-making fermentation processes, where phage attacks are of economical importance. Recent insights in their expression and mode of action indicate that, behind diverse phenotypic and molecular effects, lactococcal Abis share common traits with the well-studied Escherichia coli systems Lit and Prr. Abis are widespread in bacteria, and recent analysis indicates that Abis might have additional roles other than conferring phage resistance. - -\*\*Forde, A. & Fitzgerald, G. F. Bacteriophage defence systems in lactic acid bacteria. Antonie Van Leeuwenhoek 76, 89-113 (1999).\*\* -The study of the interactions between lactic acid bacteria and their bacteriophages has been a vibrant and rewarding research activity for a considerable number of years. In the more recent past, the application of molecular genetics for the analysis of phage-host relationships has contributed enormously to the unravelling of specific events which dictate insensitivity to bacteriophage infection and has revealed that while they are complex and intricate in nature, they are also extremely effective. In addition, the strategy has laid solid foundations for the construction of phage resistant strains for use in commercial applications and has provided a sound basis for continued investigations into existing, naturally-derived and novel, genetically-engineered defence systems. Of course, it has also become clear that phage particles are highly dynamic in their response to those defence systems which they do encounter and that they can readily adapt to them as a consequence of their genetic flexibility and plasticity. This paper reviews the exciting developments that have been described in the literature regarding the study of phage-host interactions in lactic acid bacteria and the innovative approaches that can be taken to exploit this basic information for curtailing phage infection. +::article-doi-list +--- +items: + - 10.1023/A:1002027321171 + - 10.1016/j.mib.2005.06.006 +--- +:: diff --git a/content/2.defense-systems/abiu.md b/content/2.defense-systems/abiu.md index aff2ae21c1422157434cb11d8c32eae920f34143..43cb5dbb1eff238efe5a0a07786d18454015ffbc 100644 --- a/content/2.defense-systems/abiu.md +++ b/content/2.defense-systems/abiu.md @@ -30,9 +30,11 @@ A system from \*lactococcal plasmid\* in \*lactococci\* has an anti-phage effect ## Relevant abstracts -\*\*Chopin, M.-C., Chopin, A. & Bidnenko, E. Phage abortive infection in lactococci: variations on a theme. Curr Opin Microbiol 8, 473-479 (2005).\*\* -Abortive infection (Abi) systems, also called phage exclusion, block phage multiplication and cause premature bacterial cell death upon phage infection. This decreases the number of progeny particles and limits their spread to other cells allowing the bacterial population to survive. Twenty Abi systems have been isolated in Lactococcus lactis, a bacterium used in cheese-making fermentation processes, where phage attacks are of economical importance. Recent insights in their expression and mode of action indicate that, behind diverse phenotypic and molecular effects, lactococcal Abis share common traits with the well-studied Escherichia coli systems Lit and Prr. Abis are widespread in bacteria, and recent analysis indicates that Abis might have additional roles other than conferring phage resistance. - -\*\*Forde, A. & Fitzgerald, G. F. Bacteriophage defence systems in lactic acid bacteria. Antonie Van Leeuwenhoek 76, 89-113 (1999).\*\* -The study of the interactions between lactic acid bacteria and their bacteriophages has been a vibrant and rewarding research activity for a considerable number of years. In the more recent past, the application of molecular genetics for the analysis of phage-host relationships has contributed enormously to the unravelling of specific events which dictate insensitivity to bacteriophage infection and has revealed that while they are complex and intricate in nature, they are also extremely effective. In addition, the strategy has laid solid foundations for the construction of phage resistant strains for use in commercial applications and has provided a sound basis for continued investigations into existing, naturally-derived and novel, genetically-engineered defence systems. Of course, it has also become clear that phage particles are highly dynamic in their response to those defence systems which they do encounter and that they can readily adapt to them as a consequence of their genetic flexibility and plasticity. This paper reviews the exciting developments that have been described in the literature regarding the study of phage-host interactions in lactic acid bacteria and the innovative approaches that can be taken to exploit this basic information for curtailing phage infection. +::article-doi-list +--- +items: + - 10.1023/A:1002027321171 + - 10.1016/j.mib.2005.06.006 +--- +:: diff --git a/content/2.defense-systems/abiv.md b/content/2.defense-systems/abiv.md index 22ebf6bca95c7403722f8958aedea7b79c5a83b3..89db7fa2a5fe5cf7b3d1a79fd1a52813586ee9fb 100644 --- a/content/2.defense-systems/abiv.md +++ b/content/2.defense-systems/abiv.md @@ -30,9 +30,11 @@ A system from \*Lactococcus lactis\* in \*Lactococcus lactis\* has an anti-phage ## Relevant abstracts -\*\*Forde, A. & Fitzgerald, G. F. Bacteriophage defence systems in lactic acid bacteria. Antonie Van Leeuwenhoek 76, 89-113 (1999).\*\* -The study of the interactions between lactic acid bacteria and their bacteriophages has been a vibrant and rewarding research activity for a considerable number of years. In the more recent past, the application of molecular genetics for the analysis of phage-host relationships has contributed enormously to the unravelling of specific events which dictate insensitivity to bacteriophage infection and has revealed that while they are complex and intricate in nature, they are also extremely effective. In addition, the strategy has laid solid foundations for the construction of phage resistant strains for use in commercial applications and has provided a sound basis for continued investigations into existing, naturally-derived and novel, genetically-engineered defence systems. Of course, it has also become clear that phage particles are highly dynamic in their response to those defence systems which they do encounter and that they can readily adapt to them as a consequence of their genetic flexibility and plasticity. This paper reviews the exciting developments that have been described in the literature regarding the study of phage-host interactions in lactic acid bacteria and the innovative approaches that can be taken to exploit this basic information for curtailing phage infection. - -\*\*Haaber, J., Moineau, S., Fortier, L.-C. & Hammer, K. AbiV, a Novel Antiphage Abortive Infection Mechanism on the Chromosome of Lactococcus lactis subsp. cremoris MG1363. Appl Environ Microbiol 74, 6528-6537 (2008).\*\* -Insertional mutagenesis with pGhost9::ISS1 resulted in independent insertions in a 350-bp region of the chromosome of Lactococcus lactis subsp. cremoris MG1363 that conferred phage resistance to the integrants. The orientation and location of the insertions suggested that the phage resistance phenotype was caused by a chromosomal gene turned on by a promoter from the inserted construct. Reverse transcription-PCR analysis confirmed that there were higher levels of transcription of a downstream open reading frame (ORF) in the phage-resistant integrants than in the phage-sensitive strain L. lactis MG1363. This gene was also found to confer phage resistance to L. lactis MG1363 when it was cloned into an expression vector. A subsequent frameshift mutation in the ORF completely eliminated the phage resistance phenotype, confirming that the ORF was necessary for phage resistance. This ORF provided resistance against virulent lactococcal phages belonging to the 936 and c2 species with an efficiency of plaquing of 10?4, but it did not protect against members of the P335 species. A high level of expression of the ORF did not affect the cellular growth rate. Assays for phage adsorption, DNA ejection, restriction/modification activity, plaque size, phage DNA replication, and cell survival showed that the ORF encoded an abortive infection (Abi) mechanism. Sequence analysis revealed a deduced protein consisting of 201 amino acids which, in its native state, probably forms a dimer in the cytosol. Similarity searches revealed no homology to other phage resistance mechanisms, and thus, this novel Abi mechanism was designated AbiV. The mode of action of AbiV is unknown, but the activity of AbiV prevented cleavage of the replicated phage DNA of 936-like phages. +::article-doi-list +--- +items: + - 10.1023/A:1002027321171 + - 10.1128/AEM.00780-08 +--- +:: diff --git a/content/2.defense-systems/abiz.md b/content/2.defense-systems/abiz.md index 09dde3efa98073d8a56c634e751fbfefbd64f9fc..78081068f3bedfaebcb7d7c3002f84822377323b 100644 --- a/content/2.defense-systems/abiz.md +++ b/content/2.defense-systems/abiz.md @@ -30,9 +30,11 @@ A system from \*Lactococcus lactis\* in \*Lactococcus lactis\* has an anti-phage ## Relevant abstracts -\*\*Durmaz, E. & Klaenhammer, T. R. Abortive Phage Resistance Mechanism AbiZ Speeds the Lysis Clock To Cause Premature Lysis of Phage-Infected Lactococcus lactis. J Bacteriol 189, 1417-1425 (2007).\*\* -The conjugative plasmid pTR2030 has been used extensively to confer phage resistance in commercial Lactococcus starter cultures. The plasmid harbors a 16-kb region, flanked by insertion sequence (IS) elements, that encodes the restriction/modification system LlaI and carries an abortive infection gene, abiA. The AbiA system inhibits both prolate and small isometric phages by interfering with the early stages of phage DNA replication. However, abiA alone does not account for the full abortive activity reported for pTR2030. In this study, a 7.5-kb region positioned within the IS elements and downstream of abiA was sequenced to reveal seven additional open reading frames (ORFs). A single ORF, designated abiZ, was found to be responsible for a significant reduction in plaque size and an efficiency of plaquing (EOP) of 10?6, without affecting phage adsorption. AbiZ causes phage ?31-infected Lactococcus lactis NCK203 to lyse 15 min early, reducing the burst size of ?31 100-fold. Thirteen of 14 phages of the P335 group were sensitive to AbiZ, through reduction in either plaque size, EOP, or both. The predicted AbiZ protein contains two predicted transmembrane helices but shows no significant DNA homologies. When the phage ?31 lysin and holin genes were cloned into the nisin-inducible shuttle vector pMSP3545, nisin induction of holin and lysin caused partial lysis of NCK203. In the presence of AbiZ, lysis occurred 30 min earlier. In holin-induced cells, membrane permeability as measured using propidium iodide was greater in the presence of AbiZ. These results suggest that AbiZ may interact cooperatively with holin to cause premature lysis. - -\*\*Forde, A. & Fitzgerald, G. F. Bacteriophage defence systems in lactic acid bacteria. Antonie Van Leeuwenhoek 76, 89-113 (1999).\*\* -The study of the interactions between lactic acid bacteria and their bacteriophages has been a vibrant and rewarding research activity for a considerable number of years. In the more recent past, the application of molecular genetics for the analysis of phage-host relationships has contributed enormously to the unravelling of specific events which dictate insensitivity to bacteriophage infection and has revealed that while they are complex and intricate in nature, they are also extremely effective. In addition, the strategy has laid solid foundations for the construction of phage resistant strains for use in commercial applications and has provided a sound basis for continued investigations into existing, naturally-derived and novel, genetically-engineered defence systems. Of course, it has also become clear that phage particles are highly dynamic in their response to those defence systems which they do encounter and that they can readily adapt to them as a consequence of their genetic flexibility and plasticity. This paper reviews the exciting developments that have been described in the literature regarding the study of phage-host interactions in lactic acid bacteria and the innovative approaches that can be taken to exploit this basic information for curtailing phage infection. +::article-doi-list +--- +items: + - 10.1023/A:1002027321171 + - 10.1128/JB.00904-06 +--- +:: diff --git a/content/2.defense-systems/aditi.md b/content/2.defense-systems/aditi.md index 60a83fe47ad3603fcedff8142c451d4731f8a328..bb174371f462d688420f14a39893a305846d8897 100644 --- a/content/2.defense-systems/aditi.md +++ b/content/2.defense-systems/aditi.md @@ -30,6 +30,10 @@ A system from \*Saccharibacillus kuerlensis\* in \*Bacillus subtilis\* has an an ## Relevant abstracts -\*\*Millman, A. et al. An expanded arsenal of immune systems that protect bacteria from phages. Cell Host Microbe 30, 1556-1569.e5 (2022).\*\* -Bacterial anti-phage systems are frequently clustered in microbial genomes, forming defense islands. This property enabled the recent discovery of multiple defense systems based on their genomic co-localization with known systems, but the full arsenal of anti-phage mechanisms remains unknown. We report the discovery of 21 defense systems that protect bacteria from phages, based on computational genomic analyses and phage-infection experiments. We identified multiple systems with domains involved in eukaryotic antiviral immunity, including those homologous to the ubiquitin-like ISG15 protein, dynamin-like domains, and SEFIR domains, and show their participation in bacterial defenses. Additional systems include domains predicted to manipulate DNA and RNA molecules, alongside toxin-antitoxin systems shown here to function in anti-phage defense. These systems are widely distributed in microbial genomes, and in some bacteria, they form a considerable fraction of the immune arsenal. Our data substantially expand the inventory of defense systems utilized by bacteria to counteract phage infection. +::article-doi-list +--- +items: + - 10.1016/j.chom.2022.09.017 +--- +:: diff --git a/content/2.defense-systems/avast.md b/content/2.defense-systems/avast.md index 80912d7c2bec2ffdf7a78e9a32c406bc784c9aef..adb0fc47ba44ee04888b059f38d72fbd12dd8311 100644 --- a/content/2.defense-systems/avast.md +++ b/content/2.defense-systems/avast.md @@ -89,9 +89,11 @@ Subsystem CcAvs4 with a system from \*Corallococcus coralloides\* in \*Escherich ## Relevant abstracts -\*\*Gao, L. A. et al. Prokaryotic innate immunity through pattern recognition of conserved viral proteins. Science 377, eabm4096 (2022).\*\* -Many organisms have evolved specialized immune pattern-recognition receptors, including nucleotide-binding oligomerization domain-like receptors (NLRs) of the STAND superfamily that are ubiquitous in plants, animals, and fungi. Although the roles of NLRs in eukaryotic immunity are well established, it is unknown whether prokaryotes use similar defense mechanisms. Here, we show that antiviral STAND (Avs) homologs in bacteria and archaea detect hallmark viral proteins, triggering Avs tetramerization and the activation of diverse N-terminal effector domains, including DNA endonucleases, to abrogate infection. Cryo-electron microscopy reveals that Avs sensor domains recognize conserved folds, active-site residues, and enzyme ligands, allowing a single Avs receptor to detect a wide variety of viruses. These findings extend the paradigm of pattern recognition of pathogen-specific proteins across all three domains of life. - -\*\*Gao, L. et al. Diverse enzymatic activities mediate antiviral immunity in prokaryotes. Science 369, 1077-1084 (2020).\*\* -Bacteria and archaea are frequently attacked by viruses and other mobile genetic elements and rely on dedicated antiviral defense systems, such as restriction endonucleases and CRISPR, to survive. The enormous diversity of viruses suggests that more types of defense systems exist than are currently known. By systematic defense gene prediction and heterologous reconstitution, here we discover 29 widespread antiviral gene cassettes, collectively present in 32% of all sequenced bacterial and archaeal genomes, that mediate protection against specific bacteriophages. These systems incorporate enzymatic activities not previously implicated in antiviral defense, including RNA editing and retron satellite DNA synthesis. In addition, we computationally predict a diverse set of other putative defense genes that remain to be characterized. These results highlight an immense array of molecular functions that microbes use against viruses. +::article-doi-list +--- +items: + - 10.1126/science.aba0372 + - 10.1126/science.abm4096 +--- +:: diff --git a/content/2.defense-systems/azaca.md b/content/2.defense-systems/azaca.md index 7f73642c6c405e340339559b3498ba75e4fd9b5e..b8c75a271d7b2d04c46260ca5b37bb444e33ad7d 100644 --- a/content/2.defense-systems/azaca.md +++ b/content/2.defense-systems/azaca.md @@ -32,6 +32,10 @@ A system from \*Bacillus massilioanorexius\* in \*Bacillus subtilis\* has an ant ## Relevant abstracts -\*\*Millman, A. et al. An expanded arsenal of immune systems that protect bacteria from phages. Cell Host Microbe 30, 1556-1569.e5 (2022).\*\* -Bacterial anti-phage systems are frequently clustered in microbial genomes, forming defense islands. This property enabled the recent discovery of multiple defense systems based on their genomic co-localization with known systems, but the full arsenal of anti-phage mechanisms remains unknown. We report the discovery of 21 defense systems that protect bacteria from phages, based on computational genomic analyses and phage-infection experiments. We identified multiple systems with domains involved in eukaryotic antiviral immunity, including those homologous to the ubiquitin-like ISG15 protein, dynamin-like domains, and SEFIR domains, and show their participation in bacterial defenses. Additional systems include domains predicted to manipulate DNA and RNA molecules, alongside toxin-antitoxin systems shown here to function in anti-phage defense. These systems are widely distributed in microbial genomes, and in some bacteria, they form a considerable fraction of the immune arsenal. Our data substantially expand the inventory of defense systems utilized by bacteria to counteract phage infection. +::article-doi-list +--- +items: + - 10.1016/j.chom.2022.09.017 +--- +:: diff --git a/content/2.defense-systems/borvo.md b/content/2.defense-systems/borvo.md index 69f973283f466c3ed883ccd6860e2999e0f51f28..6ec5f4c1b9fcd4590279a1ae133a299f1d8f3d53 100644 --- a/content/2.defense-systems/borvo.md +++ b/content/2.defense-systems/borvo.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Millman, A. et al. An expanded arsenal of immune systems that protect bacteria from phages. Cell Host Microbe 30, 1556-1569.e5 (2022).\*\* -Bacterial anti-phage systems are frequently clustered in microbial genomes, forming defense islands. This property enabled the recent discovery of multiple defense systems based on their genomic co-localization with known systems, but the full arsenal of anti-phage mechanisms remains unknown. We report the discovery of 21 defense systems that protect bacteria from phages, based on computational genomic analyses and phage-infection experiments. We identified multiple systems with domains involved in eukaryotic antiviral immunity, including those homologous to the ubiquitin-like ISG15 protein, dynamin-like domains, and SEFIR domains, and show their participation in bacterial defenses. Additional systems include domains predicted to manipulate DNA and RNA molecules, alongside toxin-antitoxin systems shown here to function in anti-phage defense. These systems are widely distributed in microbial genomes, and in some bacteria, they form a considerable fraction of the immune arsenal. Our data substantially expand the inventory of defense systems utilized by bacteria to counteract phage infection. +::article-doi-list +--- +items: + - 10.1016/j.chom.2022.09.017 +--- +:: diff --git a/content/2.defense-systems/bunzi.md b/content/2.defense-systems/bunzi.md index fa713137da7d1bc2a1023fc5d1027ca183ee30ec..94ec25e4a6c28828279288420d155e1b42ca2f32 100644 --- a/content/2.defense-systems/bunzi.md +++ b/content/2.defense-systems/bunzi.md @@ -30,6 +30,10 @@ A system from \*Ligilactobacillus animalis\* in \*Bacillus subtilis\* has an ant ## Relevant abstracts -\*\*Millman, A. et al. An expanded arsenal of immune systems that protect bacteria from phages. Cell Host Microbe 30, 1556-1569.e5 (2022).\*\* -Bacterial anti-phage systems are frequently clustered in microbial genomes, forming defense islands. This property enabled the recent discovery of multiple defense systems based on their genomic co-localization with known systems, but the full arsenal of anti-phage mechanisms remains unknown. We report the discovery of 21 defense systems that protect bacteria from phages, based on computational genomic analyses and phage-infection experiments. We identified multiple systems with domains involved in eukaryotic antiviral immunity, including those homologous to the ubiquitin-like ISG15 protein, dynamin-like domains, and SEFIR domains, and show their participation in bacterial defenses. Additional systems include domains predicted to manipulate DNA and RNA molecules, alongside toxin-antitoxin systems shown here to function in anti-phage defense. These systems are widely distributed in microbial genomes, and in some bacteria, they form a considerable fraction of the immune arsenal. Our data substantially expand the inventory of defense systems utilized by bacteria to counteract phage infection. +::article-doi-list +--- +items: + - 10.1016/j.chom.2022.09.017 +--- +:: diff --git a/content/2.defense-systems/cbass.md b/content/2.defense-systems/cbass.md index 0bca0ef50616240c25e6065c34493660b1ceed19..09a20ef8ffa6d24c129fe05d6600d036b5c3901d 100644 --- a/content/2.defense-systems/cbass.md +++ b/content/2.defense-systems/cbass.md @@ -48,18 +48,14 @@ A system from \*Pseudomonas aeruginosa\* in \*Pseudomonas aeruginosa\* has an an ## Relevant abstracts -\*\*Cohen, D. et al. Cyclic GMP-AMP signalling protects bacteria against viral infection. Nature 574, 691-695 (2019).\*\* -The cyclic GMP-AMP synthase (cGAS)-STING pathway is a central component of the cell-autonomous innate immune system in animals1,2. The cGAS protein is a sensor of cytosolic viral DNA and, upon sensing DNA, it produces a cyclic GMP-AMP (cGAMP) signalling molecule that binds to the STING protein and activates the immune response3-5. The production of cGAMP has also been detected in bacteria6, and has been shown, in Vibrio cholerae, to activate a phospholipase that degrades the inner bacterial membrane7. However, the biological role of cGAMP signalling in bacteria remains unknown. Here we show that cGAMP signalling is part of an antiphage defence system that is common in bacteria. This system is composed of a four-gene operon that encodes the bacterial cGAS and the associated phospholipase, as well as two enzymes with the eukaryotic-like domains E1, E2 and JAB. We show that this operon confers resistance against a wide variety of phages. Phage infection triggers the production of cGAMP, which-in turn-activates the phospholipase, leading to a loss of membrane integrity and to cell death before completion of phage reproduction. Diverged versions of this system appear in more than 10% of prokaryotic genomes, and we show that variants with effectors other than phospholipase also protect against phage infection. Our results suggest that the eukaryotic cGAS-STING antiviral pathway has ancient evolutionary roots that stem from microbial defences against phages. - -\*\*Duncan-Lowey, B., McNamara-Bordewick, N. K., Tal, N., Sorek, R. & Kranzusch, P. J. Effector-mediated membrane disruption controls cell death in CBASS antiphage defense. Molecular Cell 81, 5039-5051.e5 (2021).\*\* -Cyclic oligonucleotide-based antiphage signaling systems (CBASS) are antiviral defense operons that protect bacteria from phage replication. Here, we discover a widespread class of CBASS transmembrane (TM) effector proteins that respond to antiviral nucleotide signals and limit phage propagation through direct membrane disruption. Crystal structures of the Yersinia TM effector Cap15 reveal a compact 8-stranded ?-barrel scaffold that forms a cyclic dinucleotide receptor domain that oligomerizes upon activation. We demonstrate that activated Cap15 relocalizes throughout the cell and specifically induces rupture of the inner membrane. Screening for active effectors, we identify the function of distinct families of CBASS TM effectors and demonstrate that cell death via disruption of inner-membrane integrity is a common mechanism of defense. Our results reveal the function of the most prominent class of effector protein in CBASS immunity and define disruption of the inner membrane as a widespread strategy of abortive infection in bacterial phage defense. - -\*\*Millman, A., Melamed, S., Amitai, G. & Sorek, R. Diversity and classification of cyclic-oligonucleotide-based anti-phage signalling systems. Nat Microbiol 5, 1608-1615 (2020).\*\* -Cyclic-oligonucleotide-based anti-phage signalling systems (CBASS) are a family of defence systems against bacteriophages (hereafter phages) that share ancestry with the cGAS-STING innate immune pathway in animals. CBASS systems are composed of an oligonucleotide cyclase, which generates signalling cyclic oligonucleotides in response to phage infection, and an effector that is activated by the cyclic oligonucleotides and promotes cell death. Cell death occurs before phage replication is completed, therefore preventing the spread of phages to nearby cells. Here, we analysed 38,000 bacterial and archaeal genomes and identified more than 5,000 CBASS systems, which have diverse architectures with multiple signalling molecules, effectors and ancillary genes. We propose a classification system for CBASS that groups systems according to their operon organization, signalling molecules and effector function. Four major CBASS types were identified, sharing at least six effector subtypes that promote cell death by membrane impairment, DNA degradation or other means. We observed evidence of extensive gain and loss of CBASS systems, as well as shuffling of effector genes between systems. We expect that our classification and nomenclature scheme will guide future research in the developing CBASS field. - -\*\*Morehouse, B. R. et al. STING cyclic dinucleotide sensing originated in bacteria. Nature 586, 429-433 (2020).\*\* -Stimulator of interferon genes (STING) is a receptor in human cells that senses foreign cyclic dinucleotides that are released during bacterial infection and in endogenous cyclic GMP-AMP signalling during viral infection and anti-tumour immunity1-5. STING shares no structural homology with other known signalling proteins6-9, which has limited attempts at functional analysis and prevented explanation of the origin of cyclic dinucleotide signalling in mammalian innate immunity. Here we reveal functional STING homologues encoded within prokaryotic defence islands, as well as a conserved mechanism of signal activation. Crystal structures of bacterial STING define a minimal homodimeric scaffold that selectively responds to cyclic di-GMP synthesized by a neighbouring cGAS/DncV-like nucleotidyltransferase (CD-NTase) enzyme. Bacterial STING domains couple the recognition of cyclic dinucleotides with the formation of protein filaments to drive oligomerization of TIR effector domains and rapid NAD+ cleavage. We reconstruct the evolutionary events that followed the acquisition of STING into metazoan innate immunity, and determine the structure of a full-length TIR-STING fusion from the Pacific oyster Crassostrea gigas. Comparative structural analysis demonstrates how metazoan-specific additions to the core STING scaffold enabled a switch from direct effector function to regulation of antiviral transcription. Together, our results explain the mechanism of STING-dependent signalling and reveal the conservation of a functional cGAS-STING pathway in prokaryotic defence against bacteriophages. - -\*\*Ye, Q. et al. HORMA Domain Proteins and a Trip13-like ATPase Regulate Bacterial cGAS-like Enzymes to Mediate Bacteriophage Immunity. Mol Cell 77, 709-722.e7 (2020).\*\* -Bacteria are continually challenged by foreign invaders, including bacteriophages, and have evolved a variety of defenses against these invaders. Here, we describe the structural and biochemical mechanisms of a bacteriophage immunity pathway found in a broad array of bacteria, including E. coli and Pseudomonas aeruginosa. This pathway uses eukaryotic-like HORMA domain proteins that recognize specific peptides, then bind and activate a cGAS/DncV-like nucleotidyltransferase (CD-NTase) to generate a cyclic triadenylate (cAAA) second messenger; cAAA in turn activates an endonuclease effector, NucC. Signaling is attenuated by a homolog of the AAA+ ATPase Pch2/TRIP13, which binds and disassembles the active HORMA-CD-NTase complex. When expressed in non-pathogenic E. coli, this pathway confers immunity against bacteriophage ? through an abortive infection mechanism. Our findings reveal the molecular mechanisms of a bacterial defense pathway integrating a cGAS-like nucleotidyltransferase with HORMA domain proteins for threat sensing through protein detection and negative regulation by a Trip13 ATPase. +::article-doi-list +--- +items: + - 10.1016/j.molcel.2019.12.009 + - 10.1016/j.molcel.2021.10.020 + - 10.1038/s41564-020-0777-y + - 10.1038/s41586-019-1605-5 + - 10.1038/s41586-020-2719-5 +--- +:: diff --git a/content/2.defense-systems/dartg.md b/content/2.defense-systems/dartg.md index 69f33f63858227e5c034d6d8d3f27fe019ccea2e..2f934137fdfae023ca68ecfe1bda85c67e49f35d 100644 --- a/content/2.defense-systems/dartg.md +++ b/content/2.defense-systems/dartg.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*LeRoux, M. et al. The DarTG toxin-antitoxin system provides phage defence by ADP-ribosylating viral DNA. Nat Microbiol 7, 1028-1040 (2022).\*\* -Toxin-antitoxin (TA) systems are broadly distributed, yet poorly conserved, genetic elements whose biological functions are unclear and controversial. Some TA systems may provide bacteria with immunity to infection by their ubiquitous viral predators, bacteriophages. To identify such TA systems, we searched bioinformatically for those frequently encoded near known phage defence genes in bacterial genomes. This search identified homologues of DarTG, a recently discovered family of TA systems whose biological functions and natural activating conditions were unclear. Representatives from two different subfamilies, DarTG1 and DarTG2, strongly protected E. coli MG1655 against different phages. We demonstrate that for each system, infection with either RB69 or T5 phage, respectively, triggers release of the DarT toxin, a DNA ADP-ribosyltransferase, that then modifies viral DNA and prevents replication, thereby blocking the production of mature virions. Further, we isolated phages that have evolved to overcome DarTG defence either through mutations to their DNA polymerase or to an anti-DarT factor, gp61.2, encoded by many T-even phages. Collectively, our results indicate that phage defence may be a common function for TA systems and reveal the mechanism by which DarTG systems inhibit phage infection. +::article-doi-list +--- +items: + - 10.1038/s41564-022-01153-5 +--- +:: diff --git a/content/2.defense-systems/dazbog.md b/content/2.defense-systems/dazbog.md index 6b12aca83ad25d00f03876a7a312190e36a4f14a..ed1da650ef7f117a9c579b83cdc622c3ae5ae343 100644 --- a/content/2.defense-systems/dazbog.md +++ b/content/2.defense-systems/dazbog.md @@ -32,6 +32,10 @@ A system from \*Bacillus cereus\* in \*Bacillus subtilis\* has an anti-phage eff ## Relevant abstracts -\*\*Millman, A. et al. An expanded arsenal of immune systems that protect bacteria from phages. Cell Host Microbe 30, 1556-1569.e5 (2022).\*\* -Bacterial anti-phage systems are frequently clustered in microbial genomes, forming defense islands. This property enabled the recent discovery of multiple defense systems based on their genomic co-localization with known systems, but the full arsenal of anti-phage mechanisms remains unknown. We report the discovery of 21 defense systems that protect bacteria from phages, based on computational genomic analyses and phage-infection experiments. We identified multiple systems with domains involved in eukaryotic antiviral immunity, including those homologous to the ubiquitin-like ISG15 protein, dynamin-like domains, and SEFIR domains, and show their participation in bacterial defenses. Additional systems include domains predicted to manipulate DNA and RNA molecules, alongside toxin-antitoxin systems shown here to function in anti-phage defense. These systems are widely distributed in microbial genomes, and in some bacteria, they form a considerable fraction of the immune arsenal. Our data substantially expand the inventory of defense systems utilized by bacteria to counteract phage infection. +::article-doi-list +--- +items: + - 10.1016/j.chom.2022.09.017 +--- +:: diff --git a/content/2.defense-systems/dctpdeaminase.md b/content/2.defense-systems/dctpdeaminase.md index 850fd7d08eef34eb7807c79d9d9644e376b677f2..49403373bbe787120d8c9849824f189d593faaf8 100644 --- a/content/2.defense-systems/dctpdeaminase.md +++ b/content/2.defense-systems/dctpdeaminase.md @@ -48,9 +48,11 @@ Subsystem AvcID with a system from \*Vibrio cholerae\* in \*Escherichia coli\* h ## Relevant abstracts -\*\*Hsueh, B. Y. et al. Phage defence by deaminase-mediated depletion of deoxynucleotides in bacteria. Nat Microbiol 7, 1210-1220 (2022).\*\* -Vibrio cholerae biotype El Tor is perpetuating the longest cholera pandemic in recorded history. The genomic islands VSP-1 and VSP-2 distinguish El Tor from previous pandemic V. cholerae strains. Using a co-occurrence analysis of VSP genes in >200,000 bacterial genomes we built gene networks to infer biological functions encoded in these islands. This revealed that dncV, a component of the cyclic-oligonucleotide-based anti-phage signalling system (CBASS) anti-phage defence system, co-occurs with an uncharacterized gene vc0175 that we rename avcD for anti-viral cytodine deaminase. We show that AvcD is a deoxycytidylate deaminase and that its activity is post-translationally inhibited by a non-coding RNA named AvcI. AvcID and bacterial homologues protect bacterial populations against phage invasion by depleting free deoxycytidine nucleotides during infection, thereby decreasing phage replication. Homologues of avcD exist in all three domains of life, and bacterial AvcID defends against phage infection by combining traits of two eukaryotic innate viral immunity proteins, APOBEC and SAMHD1. - -\*\*Hsueh, B. Y. et al. Phage defence by deaminase-mediated depletion of deoxynucleotides in bacteria. Nat Microbiol 7, 1210-1220 (2022).\*\* -Vibrio cholerae biotype El Tor is perpetuating the longest cholera pandemic in recorded history. The genomic islands VSP-1 and VSP-2 distinguish El Tor from previous pandemic V. cholerae strains. Using a co-occurrence analysis of VSP genes in >200,000 bacterial genomes we built gene networks to infer biological functions encoded in these islands. This revealed that dncV, a component of the cyclic-oligonucleotide-based anti-phage signalling system (CBASS) anti-phage defence system, co-occurs with an uncharacterized gene vc0175 that we rename avcD for anti-viral cytodine deaminase. We show that AvcD is a deoxycytidylate deaminase and that its activity is post-translationally inhibited by a non-coding RNA named AvcI. AvcID and bacterial homologues protect bacterial populations against phage invasion by depleting free deoxycytidine nucleotides during infection, thereby decreasing phage replication. Homologues of avcD exist in all three domains of life, and bacterial AvcID defends against phage infection by combining traits of two eukaryotic innate viral immunity proteins, APOBEC and SAMHD1. +::article-doi-list +--- +items: + - 10.1038/s41564-022-01162-4 + - 10.1038/s41564-022-01162-4 +--- +:: diff --git a/content/2.defense-systems/dgtpase.md b/content/2.defense-systems/dgtpase.md index dbb35e955eeb9b2c367a77e271ab8bb6fd3553d3..b881eac76ff2a3d1075db41fbf71fd78fd5b5529 100644 --- a/content/2.defense-systems/dgtpase.md +++ b/content/2.defense-systems/dgtpase.md @@ -38,6 +38,10 @@ A system from \*Shewanella putrefaciens\* in \*Escherichia coli\* has an anti-ph ## Relevant abstracts -\*\*Hsueh, B. Y. et al. Phage defence by deaminase-mediated depletion of deoxynucleotides in bacteria. Nat Microbiol 7, 1210-1220 (2022).\*\* -Vibrio cholerae biotype El Tor is perpetuating the longest cholera pandemic in recorded history. The genomic islands VSP-1 and VSP-2 distinguish El Tor from previous pandemic V. cholerae strains. Using a co-occurrence analysis of VSP genes in >200,000 bacterial genomes we built gene networks to infer biological functions encoded in these islands. This revealed that dncV, a component of the cyclic-oligonucleotide-based anti-phage signalling system (CBASS) anti-phage defence system, co-occurs with an uncharacterized gene vc0175 that we rename avcD for anti-viral cytodine deaminase. We show that AvcD is a deoxycytidylate deaminase and that its activity is post-translationally inhibited by a non-coding RNA named AvcI. AvcID and bacterial homologues protect bacterial populations against phage invasion by depleting free deoxycytidine nucleotides during infection, thereby decreasing phage replication. Homologues of avcD exist in all three domains of life, and bacterial AvcID defends against phage infection by combining traits of two eukaryotic innate viral immunity proteins, APOBEC and SAMHD1. +::article-doi-list +--- +items: + - 10.1038/s41564-022-01162-4 +--- +:: diff --git a/content/2.defense-systems/disarm.md b/content/2.defense-systems/disarm.md index d40f876b5e56f9ee22c6ec7d9072308a4b9649e6..b5a7aeb8b790008f6062b8fa248e80db16e8ba8b 100644 --- a/content/2.defense-systems/disarm.md +++ b/content/2.defense-systems/disarm.md @@ -54,9 +54,11 @@ A system from \*Serratia sp. SCBI\* in \*Escherichia coli\* has an anti-phage ef ## Relevant abstracts -\*\*Bravo, J. P. K., Aparicio-Maldonado, C., Nobrega, F. L., Brouns, S. J. J. & Taylor, D. W. Structural basis for broad anti-phage immunity by DISARM. Nat Commun 13, 2987 (2022).\*\* -In the evolutionary arms race against phage, bacteria have assembled a diverse arsenal of antiviral immune strategies. While the recently discovered DISARM (Defense Island System Associated with Restriction-Modification) systems can provide protection against a wide range of phage, the molecular mechanisms that underpin broad antiviral targeting but avoiding autoimmunity remain enigmatic. Here, we report cryo-EM structures of the core DISARM complex, DrmAB, both alone and in complex with an unmethylated phage DNA mimetic. These structures reveal that DrmAB core complex is autoinhibited by a trigger loop (TL) within DrmA and binding to DNA substrates containing a 5? overhang dislodges the TL, initiating a long-range structural rearrangement for DrmAB activation. Together with structure-guided in vivo studies, our work provides insights into the mechanism of phage DNA recognition and specific activation of this widespread antiviral defense system. - -\*\*Ofir, G. et al. DISARM is a widespread bacterial defence system with broad anti-phage activities. Nat Microbiol 3, 90-98 (2018).\*\* -The evolutionary pressure imposed by phage predation on bacteria and archaea has resulted in the development of effective anti-phage defence mechanisms, including restriction-modification and CRISPR-Cas systems. Here, we report on a new defence system, DISARM (defence island system associated with restriction-modification), which is widespread in bacteria and archaea. DISARM is composed of five genes, including a DNA methylase and four other genes annotated as a helicase domain, a phospholipase D (PLD) domain, a DUF1998 domain and a gene of unknown function. Engineering the Bacillus paralicheniformis 9945a DISARM system into Bacillus subtilis has rendered the engineered bacteria protected against phages from all three major families of tailed double-stranded DNA phages. Using a series of gene deletions, we show that four of the five genes are essential for DISARM-mediated defence, with the fifth (PLD) being redundant for defence against some of the phages. We further show that DISARM restricts incoming phage DNA and that the B. paralicheniformis DISARM methylase modifies host CCWGG motifs as a marker of self DNA akin to restriction-modification systems. Our results suggest that DISARM is a new type of multi-gene restriction-modification module, expanding the arsenal of defence systems known to be at the disposal of prokaryotes against their viruses. +::article-doi-list +--- +items: + - 10.1038/s41467-022-30673-1 + - 10.1038/s41564-017-0051-0 +--- +:: diff --git a/content/2.defense-systems/dmdde.md b/content/2.defense-systems/dmdde.md index e83d0ec756702ff0524def9acf4df1f6f3d53080..3c077fd84f216b80b34324a12f8c4ecea1e356f1 100644 --- a/content/2.defense-systems/dmdde.md +++ b/content/2.defense-systems/dmdde.md @@ -24,6 +24,10 @@ Among the 22k complete genomes of RefSeq, this system is present in 145 genomes ## Relevant abstracts -\*\*Jaskólska, M., Adams, D. W. & Blokesch, M. Two defence systems eliminate plasmids from seventh pandemic Vibrio cholerae. Nature 604, 323-329 (2022).\*\* -Horizontal gene transfer can trigger rapid shifts in bacterial evolution. Driven by a variety of mobile genetic elements—in particular bacteriophages and plasmids—the ability to share genes within and across species underpins the exceptional adaptability of bacteria. Nevertheless, invasive mobile genetic elements can also present grave risks to the host; bacteria have therefore evolved a vast array of defences against these elements1. Here we identify two plasmid defence systems conserved in the Vibrio cholerae El Tor strains responsible for the ongoing seventh cholera pandemic2-4. These systems, termed DdmABC and DdmDE, are encoded on two major pathogenicity islands that are a hallmark of current pandemic strains. We show that the modules cooperate to rapidly eliminate small multicopy plasmids by degradation. Moreover, the DdmABC system is widespread and can defend against bacteriophage infection by triggering cell suicide (abortive infection, or Abi). Notably, we go on to show that, through an Abi-like mechanism, DdmABC increases the burden of large low-copy-number conjugative plasmids, including a broad-host IncC multidrug resistance plasmid, which creates a fitness disadvantage that counterselects against plasmid-carrying cells. Our results answer the long-standing question of why plasmids, although abundant in environmental strains, are rare in pandemic strains; have implications for understanding the dissemination of antibiotic resistance plasmids; and provide insights into how the interplay between two defence systems has shaped the evolution of the most successful lineage of pandemic V. cholerae. +::article-doi-list +--- +items: + - 10.1038/s41586-022-04546-y +--- +:: diff --git a/content/2.defense-systems/dnd.md b/content/2.defense-systems/dnd.md index 64d04e46b6a40db450a57cfdb7af7ec05d26c0cc..b886a21c12e13c38e098394380ebacaa3026067e 100644 --- a/content/2.defense-systems/dnd.md +++ b/content/2.defense-systems/dnd.md @@ -34,9 +34,11 @@ Subsystem DndCDEA-PbeABCD with a system from \*Halalkalicoccus jeotgali\* in \*N ## Relevant abstracts -\*\*Wang, L. et al. Phosphorothioation of DNA in bacteria by dnd genes. Nat Chem Biol 3, 709-710 (2007).\*\* -Modifications of the canonical structures of DNA and RNA play critical roles in cell physiology, DNA replication, transcription and translation in all organisms. We now report that bacterial dnd gene clusters incorporate sulfur into the DNA backbone as a sequence-selective, stereospecific phosphorothioate modification. To our knowledge, unlike any other DNA or RNA modification systems, DNA phosphorothioation by dnd gene clusters is the first physiological modification described on the DNA backbone. - -\*\*Xiong, L. et al. A new type of DNA phosphorothioation-based antiviral system in archaea. Nat Commun 10, 1688 (2019).\*\* -Archaea and Bacteria have evolved different defence strategies that target virtually all steps of the viral life cycle. The diversified virion morphotypes and genome contents of archaeal viruses result in a highly complex array of archaea-virus interactions. However, our understanding of archaeal antiviral activities lags far behind our knowledges of those in bacteria. Here we report a new archaeal defence system that involves DndCDEA-specific DNA phosphorothioate (PT) modification and the PbeABCD-mediated halt of virus propagation via inhibition of DNA replication. In contrast to the breakage of invasive DNA by DndFGH in bacteria, DndCDEA-PbeABCD does not degrade or cleave viral DNA. The PbeABCD-mediated PT defence system is widespread and exhibits extensive interdomain and intradomain gene transfer events. Our results suggest that DndCDEA-PbeABCD is a new type of PT-based virus resistance system, expanding the known arsenal of defence systems as well as our understanding of host-virus interactions. +::article-doi-list +--- +items: + - 10.1038/nchembio.2007.39 + - 10.1038/s41467-019-09390-9 +--- +:: diff --git a/content/2.defense-systems/dodola.md b/content/2.defense-systems/dodola.md index c364e2494310a7f0069e83a8a5843903952c0280..c360400445ae858f370279d59f4d51742c664ddc 100644 --- a/content/2.defense-systems/dodola.md +++ b/content/2.defense-systems/dodola.md @@ -30,6 +30,10 @@ A system from \*Bacillus cereus\* in \*Bacillus subtilis\* has an anti-phage eff ## Relevant abstracts -\*\*Millman, A. et al. An expanded arsenal of immune systems that protect bacteria from phages. Cell Host Microbe 30, 1556-1569.e5 (2022).\*\* -Bacterial anti-phage systems are frequently clustered in microbial genomes, forming defense islands. This property enabled the recent discovery of multiple defense systems based on their genomic co-localization with known systems, but the full arsenal of anti-phage mechanisms remains unknown. We report the discovery of 21 defense systems that protect bacteria from phages, based on computational genomic analyses and phage-infection experiments. We identified multiple systems with domains involved in eukaryotic antiviral immunity, including those homologous to the ubiquitin-like ISG15 protein, dynamin-like domains, and SEFIR domains, and show their participation in bacterial defenses. Additional systems include domains predicted to manipulate DNA and RNA molecules, alongside toxin-antitoxin systems shown here to function in anti-phage defense. These systems are widely distributed in microbial genomes, and in some bacteria, they form a considerable fraction of the immune arsenal. Our data substantially expand the inventory of defense systems utilized by bacteria to counteract phage infection. +::article-doi-list +--- +items: + - 10.1016/j.chom.2022.09.017 +--- +:: diff --git a/content/2.defense-systems/dpd.md b/content/2.defense-systems/dpd.md index 6061cc1a61786ef489a1ee1ebace470af56b5152..0d58f9dd993ee1d2e6572e44e5a6750e1aaf49f0 100644 --- a/content/2.defense-systems/dpd.md +++ b/content/2.defense-systems/dpd.md @@ -24,6 +24,10 @@ Among the 22k complete genomes of RefSeq, this system is present in 226 genomes ## Relevant abstracts -\*\*Thiaville, J. J. et al. Novel genomic island modifies DNA with 7-deazaguanine derivatives. Proceedings of the National Academy of Sciences 113, E1452-E1459 (2016).\*\* -The discovery of ?20-kb gene clusters containing a family of paralogs of tRNA guanosine transglycosylase genes, called tgtA5, alongside 7-cyano-7-deazaguanine (preQ0) synthesis and DNA metabolism genes, led to the hypothesis that 7-deazaguanine derivatives are inserted in DNA. This was established by detecting 2Â’-deoxy-preQ0 and 2Â’-deoxy-7-amido-7-deazaguanosine in enzymatic hydrolysates of DNA extracted from the pathogenic, Gram-negative bacteria Salmonella enterica serovar Montevideo. These modifications were absent in the closely related S. enterica serovar Typhimurium LT2 and from a mutant of S. Montevideo, each lacking the gene cluster. This led us to rename the genes of the S. Montevideo cluster as dpdA-K for 7-deazapurine in DNA. Similar gene clusters were analyzed in ?150 phylogenetically diverse bacteria, and the modifications were detected in DNA from other organisms containing these clusters, including Kineococcus radiotolerans, Comamonas testosteroni, and Sphingopyxis alaskensis. Comparative genomic analysis shows that, in Enterobacteriaceae, the cluster is a genomic island integrated at the leuX locus, and the phylogenetic analysis of the TgtA5 family is consistent with widespread horizontal gene transfer. Comparison of transformation efficiencies of modified or unmodified plasmids into isogenic S. Montevideo strains containing or lacking the cluster strongly suggests a restriction-modification role for the cluster in Enterobacteriaceae. Another preQ0 derivative, 2Â’-deoxy-7-formamidino-7-deazaguanosine, was found in the Escherichia coli bacteriophage 9g, as predicted from the presence of homologs of genes involved in the synthesis of the archaeosine tRNA modification. These results illustrate a deep and unexpected evolutionary connection between DNA and tRNA metabolism. +::article-doi-list +--- +items: + - 10.1073/pnas.1518570113 +--- +:: diff --git a/content/2.defense-systems/drt.md b/content/2.defense-systems/drt.md index 3f11fb80751cba8a419369f24cbf7ae1fad937e1..4b93d5cb0a50df5c352d736f1a2710e9bf28909a 100644 --- a/content/2.defense-systems/drt.md +++ b/content/2.defense-systems/drt.md @@ -72,9 +72,11 @@ Subsystem RT (UG28) (Type 9) with a system from \*Escherichia coli\* in \*Escher ## Relevant abstracts -\*\*Gao, L. et al. Diverse enzymatic activities mediate antiviral immunity in prokaryotes. Science 369, 1077-1084 (2020).\*\* -Bacteria and archaea are frequently attacked by viruses and other mobile genetic elements and rely on dedicated antiviral defense systems, such as restriction endonucleases and CRISPR, to survive. The enormous diversity of viruses suggests that more types of defense systems exist than are currently known. By systematic defense gene prediction and heterologous reconstitution, here we discover 29 widespread antiviral gene cassettes, collectively present in 32% of all sequenced bacterial and archaeal genomes, that mediate protection against specific bacteriophages. These systems incorporate enzymatic activities not previously implicated in antiviral defense, including RNA editing and retron satellite DNA synthesis. In addition, we computationally predict a diverse set of other putative defense genes that remain to be characterized. These results highlight an immense array of molecular functions that microbes use against viruses. - -\*\*Mestre, M. R. et al. UG/Abi: a highly diverse family of prokaryotic reverse transcriptases associated with defense functions. Nucleic Acids Research 50, 6084-6101 (2022).\*\* -Reverse transcriptases (RTs) are enzymes capable of synthesizing DNA using RNA as a template. Within the last few years, a burst of research has led to the discovery of novel prokaryotic RTs with diverse antiviral properties, such as DRTs (Defense-associated RTs), which belong to the so-called group of unknown RTs (UG) and are closely related to the Abortive Infection system (Abi) RTs. In this work, we performed a systematic analysis of UG and Abi RTs, increasing the number of UG/Abi members up to 42 highly diverse groups, most of which are predicted to be functionally associated with other gene(s) or domain(s). Based on this information, we classified these systems into three major classes. In addition, we reveal that most of these groups are associated with defense functions and/or mobile genetic elements, and demonstrate the antiphage role of four novel groups. Besides, we highlight the presence of one of these systems in novel families of human gut viruses infecting members of the Bacteroidetes and Firmicutes phyla. This work lays the foundation for a comprehensive and unified understanding of these highly diverse RTs with enormous biotechnological potential. +::article-doi-list +--- +items: + - 10.1093/nar/gkac467 + - 10.1126/science.aba0372 +--- +:: diff --git a/content/2.defense-systems/druantia.md b/content/2.defense-systems/druantia.md index c97fc8f82e006f46cbffdd03bb93d1b445feac3b..59d0afa2d95b63cbca01ecff703b66c50171d1d0 100644 --- a/content/2.defense-systems/druantia.md +++ b/content/2.defense-systems/druantia.md @@ -38,6 +38,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Doron, S. et al. Systematic discovery of antiphage defense systems in the microbial pangenome. Science 359, eaar4120 (2018).\*\* -The arms race between bacteria and phages led to the development of sophisticated antiphage defense systems, including CRISPR-Cas and restriction-modification systems. Evidence suggests that known and unknown defense systems are located in "defense islands" in microbial genomes. Here, we comprehensively characterized the bacterial defensive arsenal by examining gene families that are clustered next to known defense genes in prokaryotic genomes. Candidate defense systems were systematically engineered and validated in model bacteria for their antiphage activities. We report nine previously unknown antiphage systems and one antiplasmid system that are widespread in microbes and strongly protect against foreign invaders. These include systems that adopted components of the bacterial flagella and condensin complexes. Our data also suggest a common, ancient ancestry of innate immunity components shared between animals, plants, and bacteria. +::article-doi-list +--- +items: + - 10.1126/science.aar4120 +--- +:: diff --git a/content/2.defense-systems/dsr.md b/content/2.defense-systems/dsr.md index 28a137ee0097ff3f4f35cf2299447e85301b0feb..7b35c9cb46d526675a24fc05a0dbf4817ef7a9ef 100644 --- a/content/2.defense-systems/dsr.md +++ b/content/2.defense-systems/dsr.md @@ -40,9 +40,11 @@ Subsystem DSR1 with a system from \*Bacillus subtilis\* in \*Bacillus subtilis \ ## Relevant abstracts -\*\*Gao, L. et al. Diverse enzymatic activities mediate antiviral immunity in prokaryotes. Science 369, 1077-1084 (2020).\*\* -Bacteria and archaea are frequently attacked by viruses and other mobile genetic elements and rely on dedicated antiviral defense systems, such as restriction endonucleases and CRISPR, to survive. The enormous diversity of viruses suggests that more types of defense systems exist than are currently known. By systematic defense gene prediction and heterologous reconstitution, here we discover 29 widespread antiviral gene cassettes, collectively present in 32% of all sequenced bacterial and archaeal genomes, that mediate protection against specific bacteriophages. These systems incorporate enzymatic activities not previously implicated in antiviral defense, including RNA editing and retron satellite DNA synthesis. In addition, we computationally predict a diverse set of other putative defense genes that remain to be characterized. These results highlight an immense array of molecular functions that microbes use against viruses. - -\*\*Garb, J. et al. Multiple phage resistance systems inhibit infection via SIR2-dependent NAD+ depletion. Nat Microbiol 7, 1849-1856 (2022).\*\* -Defence-associated sirtuins (DSRs) comprise a family of proteins that defend bacteria from phage infection via an unknown mechanism. These proteins are common in bacteria and harbour an N-terminal sirtuin (SIR2) domain. In this study we report that DSR proteins degrade nicotinamide adenine dinucleotide (NAD+) during infection, depleting the cell of this essential molecule and aborting phage propagation. Our data show that one of these proteins, DSR2, directly identifies phage tail tube proteins and then becomes an active NADase in Bacillus subtilis. Using a phage mating methodology that promotes genetic exchange between pairs of DSR2-sensitive and DSR2-resistant phages, we further show that some phages express anti-DSR2 proteins that bind and repress DSR2. Finally, we demonstrate that the SIR2 domain serves as an effector NADase in a diverse set of phage defence systems outside the DSR family. Our results establish the general role of SIR2 domains in bacterial immunity against phages. +::article-doi-list +--- +items: + - 10.1038/s41564-022-01207-8 + - 10.1126/science.aba0372 +--- +:: diff --git a/content/2.defense-systems/eleos.md b/content/2.defense-systems/eleos.md index d9778bd265dc7e640da3812433db1067ca074c14..37674c2fa0df06d99c862108636dd5a495281991 100644 --- a/content/2.defense-systems/eleos.md +++ b/content/2.defense-systems/eleos.md @@ -32,5 +32,10 @@ A system from \*Bacillus vietnamensis\* in \*Bacillus subtilis\* has an anti-pha ## Relevant abstracts -\*\*Millman, A. et al. An expanded arsenal of immune systems that protect bacteria from phages. Cell Host Microbe 30, 1556-1569.e5 (2022).\*\* -Bacterial anti-phage systems are frequently clustered in microbial genomes, forming defense islands. This property enabled the recent discovery of multiple defense systems based on their genomic co-localization with known systems, but the full arsenal of anti-phage mechanisms remains unknown. We report the discovery of 21 defense systems that protect bacteria from phages, based on computational genomic analyses and phage-infection experiments. We identified multiple systems with domains involved in eukaryotic antiviral immunity, including those homologous to the ubiquitin-like ISG15 protein, dynamin-like domains, and SEFIR domains, and show their participation in bacterial defenses. Additional systems include domains predicted to manipulate DNA and RNA molecules, alongside toxin-antitoxin systems shown here to function in anti-phage defense. These systems are widely distributed in microbial genomes, and in some bacteria, they form a considerable fraction of the immune arsenal. Our data substantially expand the inventory of defense systems utilized by bacteria to counteract phage infection. +::article-doi-list +--- +items: + - 10.1016/j.chom.2022.09.017 + +--- +:: diff --git a/content/2.defense-systems/gabija.md b/content/2.defense-systems/gabija.md index 9be9795588ca7b9ca257b70afb8c1ffe97ecb4d5..dab338df4d9d347dba395aca50996b609de4d850 100644 --- a/content/2.defense-systems/gabija.md +++ b/content/2.defense-systems/gabija.md @@ -44,9 +44,11 @@ A system from \*Bacillus cereus\* in \*Escherichia coli\* has an anti-phage effe ## Relevant abstracts -\*\*Cheng, R. et al. A nucleotide-sensing endonuclease from the Gabija bacterial defense system. Nucleic Acids Res 49, 5216-5229 (2021).\*\* -The arms race between bacteria and phages has led to the development of exquisite bacterial defense systems including a number of uncharacterized systems distinct from the well-known restriction-modification and CRISPR/Cas systems. Here, we report functional analyses of the GajA protein from the newly predicted Gabija system. The GajA protein is revealed as a sequence-specific DNA nicking endonuclease unique in that its activity is strictly regulated by nucleotide concentration. NTP and dNTP at physiological concentrations can fully inhibit the robust DNA cleavage activity of GajA. Interestingly, the nucleotide inhibition is mediated by an ATPase-like domain, which usually hydrolyzes ATP to stimulate the DNA cleavage when associated with other nucleases. These features suggest a mechanism of the Gabija defense in which an endonuclease activity is suppressed under normal conditions, while it is activated by the depletion of NTP and dNTP upon the replication and transcription of invading phages. This work highlights a concise strategy to utilize a DNA nicking endonuclease for phage resistance via nucleotide regulation. - -\*\*Doron, S. et al. Systematic discovery of antiphage defense systems in the microbial pangenome. Science 359, eaar4120 (2018).\*\* -The arms race between bacteria and phages led to the development of sophisticated antiphage defense systems, including CRISPR-Cas and restriction-modification systems. Evidence suggests that known and unknown defense systems are located in "defense islands" in microbial genomes. Here, we comprehensively characterized the bacterial defensive arsenal by examining gene families that are clustered next to known defense genes in prokaryotic genomes. Candidate defense systems were systematically engineered and validated in model bacteria for their antiphage activities. We report nine previously unknown antiphage systems and one antiplasmid system that are widespread in microbes and strongly protect against foreign invaders. These include systems that adopted components of the bacterial flagella and condensin complexes. Our data also suggest a common, ancient ancestry of innate immunity components shared between animals, plants, and bacteria. +::article-doi-list +--- +items: + - 10.1093/nar/gkab277 + - 10.1126/science.aar4120 +--- +:: diff --git a/content/2.defense-systems/gao_ape.md b/content/2.defense-systems/gao_ape.md index b0148c8592cd3be3301efd887940d76efd9c8eeb..dae5c35b53479fef68d9d4236d9e6972b47e2ec9 100644 --- a/content/2.defense-systems/gao_ape.md +++ b/content/2.defense-systems/gao_ape.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Gao, L. et al. Diverse enzymatic activities mediate antiviral immunity in prokaryotes. Science 369, 1077-1084 (2020).\*\* -Bacteria and archaea are frequently attacked by viruses and other mobile genetic elements and rely on dedicated antiviral defense systems, such as restriction endonucleases and CRISPR, to survive. The enormous diversity of viruses suggests that more types of defense systems exist than are currently known. By systematic defense gene prediction and heterologous reconstitution, here we discover 29 widespread antiviral gene cassettes, collectively present in 32% of all sequenced bacterial and archaeal genomes, that mediate protection against specific bacteriophages. These systems incorporate enzymatic activities not previously implicated in antiviral defense, including RNA editing and retron satellite DNA synthesis. In addition, we computationally predict a diverse set of other putative defense genes that remain to be characterized. These results highlight an immense array of molecular functions that microbes use against viruses. +::article-doi-list +--- +items: + - 10.1126/science.aba0372 +--- +:: diff --git a/content/2.defense-systems/gao_her.md b/content/2.defense-systems/gao_her.md index 7d0298c289d1fed800337595ba8fc865ec96ba28..3ac030b07accd0df49f233aa945d4aa5ff33b635 100644 --- a/content/2.defense-systems/gao_her.md +++ b/content/2.defense-systems/gao_her.md @@ -36,6 +36,10 @@ Subsystem DUF4297 + HerA with a system from \*Escherichia coli\* in \*Escherichi ## Relevant abstracts -\*\*Gao, L. et al. Diverse enzymatic activities mediate antiviral immunity in prokaryotes. Science 369, 1077-1084 (2020).\*\* -Bacteria and archaea are frequently attacked by viruses and other mobile genetic elements and rely on dedicated antiviral defense systems, such as restriction endonucleases and CRISPR, to survive. The enormous diversity of viruses suggests that more types of defense systems exist than are currently known. By systematic defense gene prediction and heterologous reconstitution, here we discover 29 widespread antiviral gene cassettes, collectively present in 32% of all sequenced bacterial and archaeal genomes, that mediate protection against specific bacteriophages. These systems incorporate enzymatic activities not previously implicated in antiviral defense, including RNA editing and retron satellite DNA synthesis. In addition, we computationally predict a diverse set of other putative defense genes that remain to be characterized. These results highlight an immense array of molecular functions that microbes use against viruses. +::article-doi-list +--- +items: + - 10.1126/science.aba0372 +--- +:: diff --git a/content/2.defense-systems/gao_hhe.md b/content/2.defense-systems/gao_hhe.md index f15521a0816154ee41f7ea2f037276193ebac580..ddef56f4bf284d4538e0d7a3232f7f0777d62d4b 100644 --- a/content/2.defense-systems/gao_hhe.md +++ b/content/2.defense-systems/gao_hhe.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Gao, L. et al. Diverse enzymatic activities mediate antiviral immunity in prokaryotes. Science 369, 1077-1084 (2020).\*\* -Bacteria and archaea are frequently attacked by viruses and other mobile genetic elements and rely on dedicated antiviral defense systems, such as restriction endonucleases and CRISPR, to survive. The enormous diversity of viruses suggests that more types of defense systems exist than are currently known. By systematic defense gene prediction and heterologous reconstitution, here we discover 29 widespread antiviral gene cassettes, collectively present in 32% of all sequenced bacterial and archaeal genomes, that mediate protection against specific bacteriophages. These systems incorporate enzymatic activities not previously implicated in antiviral defense, including RNA editing and retron satellite DNA synthesis. In addition, we computationally predict a diverse set of other putative defense genes that remain to be characterized. These results highlight an immense array of molecular functions that microbes use against viruses. +::article-doi-list +--- +items: + - 10.1126/science.aba0372 +--- +:: diff --git a/content/2.defense-systems/gao_iet.md b/content/2.defense-systems/gao_iet.md index 9fb5adbb9492ed24dd4326f1a2bbde256ff206ad..6e0fe35cb30591fcd237843b4f9f5271511d5260 100644 --- a/content/2.defense-systems/gao_iet.md +++ b/content/2.defense-systems/gao_iet.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Gao, L. et al. Diverse enzymatic activities mediate antiviral immunity in prokaryotes. Science 369, 1077-1084 (2020).\*\* -Bacteria and archaea are frequently attacked by viruses and other mobile genetic elements and rely on dedicated antiviral defense systems, such as restriction endonucleases and CRISPR, to survive. The enormous diversity of viruses suggests that more types of defense systems exist than are currently known. By systematic defense gene prediction and heterologous reconstitution, here we discover 29 widespread antiviral gene cassettes, collectively present in 32% of all sequenced bacterial and archaeal genomes, that mediate protection against specific bacteriophages. These systems incorporate enzymatic activities not previously implicated in antiviral defense, including RNA editing and retron satellite DNA synthesis. In addition, we computationally predict a diverse set of other putative defense genes that remain to be characterized. These results highlight an immense array of molecular functions that microbes use against viruses. +::article-doi-list +--- +items: + - 10.1126/science.aba0372 +--- +:: diff --git a/content/2.defense-systems/gao_mza.md b/content/2.defense-systems/gao_mza.md index e9e294c8d9bc223e121af90e33eda5805bda9a91..8da2536c99fdf5d5572d3cd54999334742c090b8 100644 --- a/content/2.defense-systems/gao_mza.md +++ b/content/2.defense-systems/gao_mza.md @@ -30,6 +30,10 @@ A system from \*Salmonella enterica\* in \*Escherichia coli\* has an anti-phage ## Relevant abstracts -\*\*Gao, L. et al. Diverse enzymatic activities mediate antiviral immunity in prokaryotes. Science 369, 1077-1084 (2020).\*\* -Bacteria and archaea are frequently attacked by viruses and other mobile genetic elements and rely on dedicated antiviral defense systems, such as restriction endonucleases and CRISPR, to survive. The enormous diversity of viruses suggests that more types of defense systems exist than are currently known. By systematic defense gene prediction and heterologous reconstitution, here we discover 29 widespread antiviral gene cassettes, collectively present in 32% of all sequenced bacterial and archaeal genomes, that mediate protection against specific bacteriophages. These systems incorporate enzymatic activities not previously implicated in antiviral defense, including RNA editing and retron satellite DNA synthesis. In addition, we computationally predict a diverse set of other putative defense genes that remain to be characterized. These results highlight an immense array of molecular functions that microbes use against viruses. +::article-doi-list +--- +items: + - 10.1126/science.aba0372 +--- +:: diff --git a/content/2.defense-systems/gao_ppl.md b/content/2.defense-systems/gao_ppl.md index 445d898231815262815d6d88a656be1e35bbefc2..17be4cc597a3b7af59a17441e74e3be7f40a5557 100644 --- a/content/2.defense-systems/gao_ppl.md +++ b/content/2.defense-systems/gao_ppl.md @@ -30,6 +30,10 @@ A system from \*Salmonella enterica\* in \*Escherichia coli\* has an anti-phage ## Relevant abstracts -\*\*Gao, L. et al. Diverse enzymatic activities mediate antiviral immunity in prokaryotes. Science 369, 1077-1084 (2020).\*\* -Bacteria and archaea are frequently attacked by viruses and other mobile genetic elements and rely on dedicated antiviral defense systems, such as restriction endonucleases and CRISPR, to survive. The enormous diversity of viruses suggests that more types of defense systems exist than are currently known. By systematic defense gene prediction and heterologous reconstitution, here we discover 29 widespread antiviral gene cassettes, collectively present in 32% of all sequenced bacterial and archaeal genomes, that mediate protection against specific bacteriophages. These systems incorporate enzymatic activities not previously implicated in antiviral defense, including RNA editing and retron satellite DNA synthesis. In addition, we computationally predict a diverse set of other putative defense genes that remain to be characterized. These results highlight an immense array of molecular functions that microbes use against viruses. +::article-doi-list +--- +items: + - 10.1126/science.aba0372 +--- +:: diff --git a/content/2.defense-systems/gao_qat.md b/content/2.defense-systems/gao_qat.md index f73ed4b9e509565c8d5436f6091a5e693b498f16..59868acc0b45a86ce68eafc808d0efa2e9e37281 100644 --- a/content/2.defense-systems/gao_qat.md +++ b/content/2.defense-systems/gao_qat.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Gao, L. et al. Diverse enzymatic activities mediate antiviral immunity in prokaryotes. Science 369, 1077-1084 (2020).\*\* -Bacteria and archaea are frequently attacked by viruses and other mobile genetic elements and rely on dedicated antiviral defense systems, such as restriction endonucleases and CRISPR, to survive. The enormous diversity of viruses suggests that more types of defense systems exist than are currently known. By systematic defense gene prediction and heterologous reconstitution, here we discover 29 widespread antiviral gene cassettes, collectively present in 32% of all sequenced bacterial and archaeal genomes, that mediate protection against specific bacteriophages. These systems incorporate enzymatic activities not previously implicated in antiviral defense, including RNA editing and retron satellite DNA synthesis. In addition, we computationally predict a diverse set of other putative defense genes that remain to be characterized. These results highlight an immense array of molecular functions that microbes use against viruses. +::article-doi-list +--- +items: + - 10.1126/science.aba0372 +--- +:: diff --git a/content/2.defense-systems/gao_rl.md b/content/2.defense-systems/gao_rl.md index 034601b539f2e6b5d6ceccbc1a0ab4a567ab531a..dac746a4f778cc366194cbc8d1474cb60527f831 100644 --- a/content/2.defense-systems/gao_rl.md +++ b/content/2.defense-systems/gao_rl.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Gao, L. et al. Diverse enzymatic activities mediate antiviral immunity in prokaryotes. Science 369, 1077-1084 (2020).\*\* -Bacteria and archaea are frequently attacked by viruses and other mobile genetic elements and rely on dedicated antiviral defense systems, such as restriction endonucleases and CRISPR, to survive. The enormous diversity of viruses suggests that more types of defense systems exist than are currently known. By systematic defense gene prediction and heterologous reconstitution, here we discover 29 widespread antiviral gene cassettes, collectively present in 32% of all sequenced bacterial and archaeal genomes, that mediate protection against specific bacteriophages. These systems incorporate enzymatic activities not previously implicated in antiviral defense, including RNA editing and retron satellite DNA synthesis. In addition, we computationally predict a diverse set of other putative defense genes that remain to be characterized. These results highlight an immense array of molecular functions that microbes use against viruses. +::article-doi-list +--- +items: + - 10.1126/science.aba0372 +--- +:: diff --git a/content/2.defense-systems/gao_tery.md b/content/2.defense-systems/gao_tery.md index 97f64384ab4699b4e1f79ebf1a73a56447e4740a..53311528a9c5761cd88abb01b40857625233dc28 100644 --- a/content/2.defense-systems/gao_tery.md +++ b/content/2.defense-systems/gao_tery.md @@ -30,6 +30,10 @@ A system from \*Citrobacter gillenii\* in \*Escherichia coli\* has an anti-phage ## Relevant abstracts -\*\*Gao, L. et al. Diverse enzymatic activities mediate antiviral immunity in prokaryotes. Science 369, 1077-1084 (2020).\*\* -Bacteria and archaea are frequently attacked by viruses and other mobile genetic elements and rely on dedicated antiviral defense systems, such as restriction endonucleases and CRISPR, to survive. The enormous diversity of viruses suggests that more types of defense systems exist than are currently known. By systematic defense gene prediction and heterologous reconstitution, here we discover 29 widespread antiviral gene cassettes, collectively present in 32% of all sequenced bacterial and archaeal genomes, that mediate protection against specific bacteriophages. These systems incorporate enzymatic activities not previously implicated in antiviral defense, including RNA editing and retron satellite DNA synthesis. In addition, we computationally predict a diverse set of other putative defense genes that remain to be characterized. These results highlight an immense array of molecular functions that microbes use against viruses. +::article-doi-list +--- +items: + - 10.1126/science.aba0372 +--- +:: diff --git a/content/2.defense-systems/gao_tmn.md b/content/2.defense-systems/gao_tmn.md index 7b691e8bca3436e725310e4d3052848bec7f3d56..ad91d33d1a3ee810095c7726b5999de83e5638d1 100644 --- a/content/2.defense-systems/gao_tmn.md +++ b/content/2.defense-systems/gao_tmn.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Gao, L. et al. Diverse enzymatic activities mediate antiviral immunity in prokaryotes. Science 369, 1077-1084 (2020).\*\* -Bacteria and archaea are frequently attacked by viruses and other mobile genetic elements and rely on dedicated antiviral defense systems, such as restriction endonucleases and CRISPR, to survive. The enormous diversity of viruses suggests that more types of defense systems exist than are currently known. By systematic defense gene prediction and heterologous reconstitution, here we discover 29 widespread antiviral gene cassettes, collectively present in 32% of all sequenced bacterial and archaeal genomes, that mediate protection against specific bacteriophages. These systems incorporate enzymatic activities not previously implicated in antiviral defense, including RNA editing and retron satellite DNA synthesis. In addition, we computationally predict a diverse set of other putative defense genes that remain to be characterized. These results highlight an immense array of molecular functions that microbes use against viruses. +::article-doi-list +--- +items: + - 10.1126/science.aba0372 +--- +:: diff --git a/content/2.defense-systems/gao_upx.md b/content/2.defense-systems/gao_upx.md index 6756f417d3a0faca2cf2a605f0c4cff426e17504..f6ff2758d0ff8d10e2d2814d52dbbb2a92973e47 100644 --- a/content/2.defense-systems/gao_upx.md +++ b/content/2.defense-systems/gao_upx.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Gao, L. et al. Diverse enzymatic activities mediate antiviral immunity in prokaryotes. Science 369, 1077-1084 (2020).\*\* -Bacteria and archaea are frequently attacked by viruses and other mobile genetic elements and rely on dedicated antiviral defense systems, such as restriction endonucleases and CRISPR, to survive. The enormous diversity of viruses suggests that more types of defense systems exist than are currently known. By systematic defense gene prediction and heterologous reconstitution, here we discover 29 widespread antiviral gene cassettes, collectively present in 32% of all sequenced bacterial and archaeal genomes, that mediate protection against specific bacteriophages. These systems incorporate enzymatic activities not previously implicated in antiviral defense, including RNA editing and retron satellite DNA synthesis. In addition, we computationally predict a diverse set of other putative defense genes that remain to be characterized. These results highlight an immense array of molecular functions that microbes use against viruses. +::article-doi-list +--- +items: + - 10.1126/science.aba0372 +--- +:: diff --git a/content/2.defense-systems/gasdermin.md b/content/2.defense-systems/gasdermin.md index 34c54eed0e5a25d9848acb7fcb55c3470057f1e6..d97a5221eff3d99f9beed54f37b5d03286ef6038 100644 --- a/content/2.defense-systems/gasdermin.md +++ b/content/2.defense-systems/gasdermin.md @@ -30,6 +30,10 @@ A system from \*Lysobacter enzymogenes\* in \*Escherichia coli\* has an anti-pha ## Relevant abstracts -\*\*Johnson, A. G. et al. Bacterial gasdermins reveal an ancient mechanism of cell death. Science 375, 221-225 (2022).\*\* -Gasdermin proteins form large membrane pores in human cells that release immune cytokines and induce lytic cell death. Gasdermin pore formation is triggered by caspase-mediated cleavage during inflammasome signaling and is critical for defense against pathogens and cancer. We discovered gasdermin homologs encoded in bacteria that defended against phages and executed cell death. Structures of bacterial gasdermins revealed a conserved pore-forming domain that was stabilized in the inactive state with a buried lipid modification. Bacterial gasdermins were activated by dedicated caspase-like proteases that catalyzed site-specific cleavage and the removal of an inhibitory C-terminal peptide. Release of autoinhibition induced the assembly of large and heterogeneous pores that disrupted membrane integrity. Thus, pyroptosis is an ancient form of regulated cell death shared between bacteria and animals. +::article-doi-list +--- +items: + - 10.1126/science.abj8432 +--- +:: diff --git a/content/2.defense-systems/gp29_gp30.md b/content/2.defense-systems/gp29_gp30.md index 869a5a8289f0cb77dbe54fc934de6c199d0a145c..9f7e24fa31ec86d2444cbf693a8792d6d8c191a9 100644 --- a/content/2.defense-systems/gp29_gp30.md +++ b/content/2.defense-systems/gp29_gp30.md @@ -24,6 +24,10 @@ Among the 22k complete genomes of RefSeq, this system is present in 314 genomes ## Relevant abstracts -\*\*Dedrick, R. M. et al. Prophage-mediated defence against viral attack and viral counter-defence. Nat Microbiol 2, 1-13 (2017).\*\* -Temperate phages are common, and prophages are abundant residents of sequenced bacterial genomes. Mycobacteriophages are viruses that infect mycobacterial hosts including Mycobacterium tuberculosis and Mycobacterium smegmatis, encompass substantial genetic diversity and are commonly temperate. Characterization of ten Cluster N temperate mycobacteriophages revealed at least five distinct prophage-expressed viral defence systems that interfere with the infection of lytic and temperate phages that are either closely related (homotypic defence) or unrelated (heterotypic defence) to the prophage. Target specificity is unpredictable, ranging from a single target phage to one-third of those tested. The defence systems include a single-subunit restriction system, a heterotypic exclusion system and a predicted (p)ppGpp synthetase, which blocks lytic phage growth, promotes bacterial survival and enables efficient lysogeny. The predicted (p)ppGpp synthetase coded by the Phrann prophage defends against phage Tweety infection, but Tweety codes for a tetrapeptide repeat protein, gp54, which acts as a highly effective counter-defence system. Prophage-mediated viral defence offers an efficient mechanism for bacterial success in host-virus dynamics, and counter-defence promotes phage co-evolution. +::article-doi-list +--- +items: + - 10.1038/nmicrobiol.2016.251 +--- +:: diff --git a/content/2.defense-systems/isg15-like.md b/content/2.defense-systems/isg15-like.md index 3665df566655a53a69ffe5384f705959409b1d0d..d00ef02a978c233281557464d0e8dac11413ea37 100644 --- a/content/2.defense-systems/isg15-like.md +++ b/content/2.defense-systems/isg15-like.md @@ -38,6 +38,10 @@ A system from \*Thiomonas sp. FB-6\* in \*Escherichia coli\* has an anti-phage e ## Relevant abstracts -\*\*Millman, A. et al. An expanded arsenal of immune systems that protect bacteria from phages. Cell Host Microbe 30, 1556-1569.e5 (2022).\*\* -Bacterial anti-phage systems are frequently clustered in microbial genomes, forming defense islands. This property enabled the recent discovery of multiple defense systems based on their genomic co-localization with known systems, but the full arsenal of anti-phage mechanisms remains unknown. We report the discovery of 21 defense systems that protect bacteria from phages, based on computational genomic analyses and phage-infection experiments. We identified multiple systems with domains involved in eukaryotic antiviral immunity, including those homologous to the ubiquitin-like ISG15 protein, dynamin-like domains, and SEFIR domains, and show their participation in bacterial defenses. Additional systems include domains predicted to manipulate DNA and RNA molecules, alongside toxin-antitoxin systems shown here to function in anti-phage defense. These systems are widely distributed in microbial genomes, and in some bacteria, they form a considerable fraction of the immune arsenal. Our data substantially expand the inventory of defense systems utilized by bacteria to counteract phage infection. +::article-doi-list +--- +items: + - 10.1016/j.chom.2022.09.017 +--- +:: diff --git a/content/2.defense-systems/kiwa.md b/content/2.defense-systems/kiwa.md index 24ebd95da275f8bcb800e106115383057a95ded7..e6059e93f0c7b9e5d299d1248a357160f8ea3c31 100644 --- a/content/2.defense-systems/kiwa.md +++ b/content/2.defense-systems/kiwa.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Doron, S. et al. Systematic discovery of antiphage defense systems in the microbial pangenome. Science 359, eaar4120 (2018).\*\* -The arms race between bacteria and phages led to the development of sophisticated antiphage defense systems, including CRISPR-Cas and restriction-modification systems. Evidence suggests that known and unknown defense systems are located in "defense islands" in microbial genomes. Here, we comprehensively characterized the bacterial defensive arsenal by examining gene families that are clustered next to known defense genes in prokaryotic genomes. Candidate defense systems were systematically engineered and validated in model bacteria for their antiphage activities. We report nine previously unknown antiphage systems and one antiplasmid system that are widespread in microbes and strongly protect against foreign invaders. These include systems that adopted components of the bacterial flagella and condensin complexes. Our data also suggest a common, ancient ancestry of innate immunity components shared between animals, plants, and bacteria. +::article-doi-list +--- +items: + - 10.1126/science.aar4120 +--- +:: diff --git a/content/2.defense-systems/lit.md b/content/2.defense-systems/lit.md index e2e5d850f385742d109a059d2cebd534658ae7a1..d5b1dffe6ca9008e9f4ea326cf8b765e50af52db 100644 --- a/content/2.defense-systems/lit.md +++ b/content/2.defense-systems/lit.md @@ -30,12 +30,12 @@ A system from \*Escherichia coli defective prophage e14\* in \*Escherichia coli\ ## Relevant abstracts -\*\*Bingham, R., Ekunwe, S. I., Falk, S., Snyder, L. & Kleanthous, C. The major head protein of bacteriophage T4 binds specifically to elongation factor Tu. J Biol Chem 275, 23219-23226 (2000).\*\* -The Lit protease in Escherichia coli K-12 strains induces cell death in response to bacteriophage T4 infection by cleaving translation elongation factor (EF) Tu and shutting down translation. Suicide of the cell is timed to the appearance late in the maturation of the phage of a short peptide sequence in the major head protein, the Gol peptide, which activates proteolysis. In the present work we demonstrate that the Gol peptide binds specifically to domains II and III of EF-Tu, creating the unique substrate for the Lit protease, which then cleaves domain I, the guanine nucleotide binding domain. The conformation of EF-Tu is important for binding and Lit cleavage, because both are sensitive to the identity of the bound nucleotide, with GDP being preferred over GTP. We propose that association of the T4 coat protein with EF-Tu plays a role in phage head assembly but that this association marks infected cells for suicide when Lit is present. Based on these data and recent observations on human immunodeficiency virus type 1 maturation, we speculate that associations between host translation factors and coat proteins may be integral to viral assembly in both prokaryotes and eukaryotes. - -\*\*Uzan, M. & Miller, E. S. Post-transcriptional control by bacteriophage T4: mRNA decay and inhibition of translation initiation. Virology Journal 7, 360 (2010).\*\* -Over 50 years of biological research with bacteriophage T4 includes notable discoveries in post-transcriptional control, including the genetic code, mRNA, and tRNA; the very foundations of molecular biology. In this review we compile the past 10 - 15 year literature on RNA-protein interactions with T4 and some of its related phages, with particular focus on advances in mRNA decay and processing, and on translational repression. Binding of T4 proteins RegB, RegA, gp32 and gp43 to their cognate target RNAs has been characterized. For several of these, further study is needed for an atomic-level perspective, where resolved structures of RNA-protein complexes are awaiting investigation. Other features of post-transcriptional control are also summarized. These include: RNA structure at translation initiation regions that either inhibit or promote translation initiation; programmed translational bypassing, where T4 orchestrates ribosome bypass of a 50 nucleotide mRNA sequence; phage exclusion systems that involve T4-mediated activation of a latent endoribonuclease (PrrC) and cofactor-assisted activation of EF-Tu proteolysis (Gol-Lit); and potentially important findings on ADP-ribosylation (by Alt and Mod enzymes) of ribosome-associated proteins that might broadly impact protein synthesis in the infected cell. Many of these problems can continue to be addressed with T4, whereas the growing database of T4-related phage genome sequences provides new resources and potentially new phage-host systems to extend the work into a broader biological, evolutionary context. - -\*\*Yu, Y. T. & Snyder, L. Translation elongation factor Tu cleaved by a phage-exclusion system. Proc Natl Acad Sci U S A 91, 802-806 (1994).\*\* -Bacteriophage T4 multiples poorly in Escherichia coli strains carrying the defective prophage, e14; the e14 prophage contains the lit gene for late inhibitor of T4 in E. coli. The exclusion is caused by the interaction of the e14-encoded protein, Lit, with a short RNA or polypeptide sequence encoded by gol from within the major head protein gene of T4. The interaction between Lit and the gol product causes a severe inhibition of all translation and prevents the transcription of genes downstream of the gol site in the same transcription unit. However, it does not inhibit most transcription, nor does it inhibit replication or affect intracellular levels of ATP. Here we show that the interaction of gol with Lit causes the cleavage of translation elongation factor Tu (EF-Tu) in a region highly conserved from bacteria to humans. The depletion of EF-Tu is at least partly responsible for the inhibition of translation and the phage exclusion. The only other phage-exclusion system to be understood in any detail also attacks a highly conserved cellular component, suggesting that phage-exclusion systems may yield important reagents for studying cellular processes. +::article-doi-list +--- +items: + - 10.1073/pnas.91.2.802 + - 10.1074/jbc.M002546200 + - 10.1186/1743-422X-7-360 +--- +:: diff --git a/content/2.defense-systems/menshen.md b/content/2.defense-systems/menshen.md index 210145d6cf1120987620b2373057ad70f91a6653..6c8d680c02249460ccaaa996b9f3bc902c8b37d2 100644 --- a/content/2.defense-systems/menshen.md +++ b/content/2.defense-systems/menshen.md @@ -32,6 +32,10 @@ A system from \*Solibacillus silvestris\* in \*Bacillus subtilis\* has an anti-p ## Relevant abstracts -\*\*Millman, A. et al. An expanded arsenal of immune systems that protect bacteria from phages. Cell Host Microbe 30, 1556-1569.e5 (2022).\*\* -Bacterial anti-phage systems are frequently clustered in microbial genomes, forming defense islands. This property enabled the recent discovery of multiple defense systems based on their genomic co-localization with known systems, but the full arsenal of anti-phage mechanisms remains unknown. We report the discovery of 21 defense systems that protect bacteria from phages, based on computational genomic analyses and phage-infection experiments. We identified multiple systems with domains involved in eukaryotic antiviral immunity, including those homologous to the ubiquitin-like ISG15 protein, dynamin-like domains, and SEFIR domains, and show their participation in bacterial defenses. Additional systems include domains predicted to manipulate DNA and RNA molecules, alongside toxin-antitoxin systems shown here to function in anti-phage defense. These systems are widely distributed in microbial genomes, and in some bacteria, they form a considerable fraction of the immune arsenal. Our data substantially expand the inventory of defense systems utilized by bacteria to counteract phage infection. +::article-doi-list +--- +items: + - 10.1016/j.chom.2022.09.017 +--- +:: diff --git a/content/2.defense-systems/mok_hok_sok.md b/content/2.defense-systems/mok_hok_sok.md index c013ad983073713d5b00b6382c8c5a9b450f0e17..89d441156e9bc732ad80d92ecf69f996fe435d2d 100644 --- a/content/2.defense-systems/mok_hok_sok.md +++ b/content/2.defense-systems/mok_hok_sok.md @@ -30,6 +30,10 @@ A system from \*R1 plasmid of Salmonella paratyphi\* in \*Escherichia coli\* has ## Relevant abstracts -\*\*Pecota, D. C. & Wood, T. K. Exclusion of T4 phage by the hok/sok killer locus from plasmid R1. Journal of Bacteriology 178, 2044 (1996).\*\* -The hok (host killing) and sok (suppressor of killing) genes (hok/sok) efficiently maintain the low-copy-number plasmid R1. To investigate whether the hok/sok locus evolved as a phage-exclusion mechanism, Escherichia coli cells that contain hok/sok on ... +::article-doi-list +--- +items: + - 10.1128/jb.178.7.2044-2050.1996 +--- +:: diff --git a/content/2.defense-systems/mokosh.md b/content/2.defense-systems/mokosh.md index aebf20b55012739616da6b6ca8b1dd9df0ee52a3..f562ef047f386519c26a43909938bbe68f0ae786 100644 --- a/content/2.defense-systems/mokosh.md +++ b/content/2.defense-systems/mokosh.md @@ -36,6 +36,10 @@ Subsystem Type II with a system from \*Escherichia coli\* in \*Escherichia coli\ ## Relevant abstracts -\*\*Millman, A. et al. An expanded arsenal of immune systems that protect bacteria from phages. Cell Host Microbe 30, 1556-1569.e5 (2022).\*\* -Bacterial anti-phage systems are frequently clustered in microbial genomes, forming defense islands. This property enabled the recent discovery of multiple defense systems based on their genomic co-localization with known systems, but the full arsenal of anti-phage mechanisms remains unknown. We report the discovery of 21 defense systems that protect bacteria from phages, based on computational genomic analyses and phage-infection experiments. We identified multiple systems with domains involved in eukaryotic antiviral immunity, including those homologous to the ubiquitin-like ISG15 protein, dynamin-like domains, and SEFIR domains, and show their participation in bacterial defenses. Additional systems include domains predicted to manipulate DNA and RNA molecules, alongside toxin-antitoxin systems shown here to function in anti-phage defense. These systems are widely distributed in microbial genomes, and in some bacteria, they form a considerable fraction of the immune arsenal. Our data substantially expand the inventory of defense systems utilized by bacteria to counteract phage infection. +::article-doi-list +--- +items: + - 10.1016/j.chom.2022.09.017 +--- +:: diff --git a/content/2.defense-systems/nhi.md b/content/2.defense-systems/nhi.md index a291e8c267c4af817ab40240fe74d73257d6f1be..1652fa61635d4444fda0309d5db514f74430e029 100644 --- a/content/2.defense-systems/nhi.md +++ b/content/2.defense-systems/nhi.md @@ -38,6 +38,10 @@ A system from \*Vibrio vulnificus\* in \*Staphylococcus aureus\* has an anti-pha ## Relevant abstracts -\*\*Bari, S. M. N. et al. A unique mode of nucleic acid immunity performed by a multifunctional bacterial enzyme. Cell Host Microbe 30, 570-582.e7 (2022).\*\* -The perpetual arms race between bacteria and their viruses (phages) has given rise to diverse immune systems, including restriction-modification and CRISPR-Cas, which sense and degrade phage-derived nucleic acids. These complex systems rely upon production and maintenance of multiple components to achieve antiphage defense. However, the prevalence and effectiveness of minimal, single-component systems that cleave DNA remain unknown. Here, we describe a unique mode of nucleic acid immunity mediated by a single enzyme with nuclease and helicase activities, herein referred to as Nhi (nuclease-helicase immunity). This enzyme provides robust protection against diverse staphylococcal phages and prevents phage DNA accumulation in cells stripped of all other known defenses. Our observations support a model in which Nhi targets and degrades phage-specific replication intermediates. Importantly, Nhi homologs are distributed in diverse bacteria and exhibit functional conservation, highlighting the versatility of such compact weapons as major players in antiphage defense. +::article-doi-list +--- +items: + - 10.1016/j.chom.2022.03.001 +--- +:: diff --git a/content/2.defense-systems/nixi.md b/content/2.defense-systems/nixi.md index b1c51cef15e20bf08780eb6916e1a5a0a8565b36..a40033ee7f32565b3039d5a776a203a9492e5d47 100644 --- a/content/2.defense-systems/nixi.md +++ b/content/2.defense-systems/nixi.md @@ -30,6 +30,10 @@ A system from \*Vibrio cholerae\* in \*Vibrio cholerae\* has an anti-phage effec ## Relevant abstracts -\*\*LeGault, K. N., Barth, Z. K., DePaola, P. & Seed, K. D. A phage parasite deploys a nicking nuclease effector to inhibit replication of its viral host. 2021.07.12.452122 Preprint at https://doi.org/10.1101/2021.07.12.452122 (2021).\*\* -PLEs are phage parasites integrated into the chromosome of epidemic Vibrio cholerae. In response to infection by its viral host ICP1, PLE excises, replicates and hijacks ICP1 structural components for transduction. Through an unknown mechanism PLE prevents ICP1 from transitioning to rolling circle replication (RCR), a prerequisite for efficient packaging of the viral genome. Here, we characterize a PLE-encoded nuclease, NixI, that blocks phage development likely by nicking ICP1Â’s genome as it transitions to RCR. NixI-dependent cleavage sites appear in ICP1Â’s genome during infection of PLE(+) V. cholerae. Purified NixI demonstrates in vitro specificity for sites in ICP1Â’s genome and NixI activity is enhanced by a putative specificity determinant co-expressed with NixI during phage infection. Importantly, NixI is sufficient to limit ICP1 genome replication and eliminate progeny production. We identify distant NixI homologs in an expanded family of putative phage satellites in Vibrios that lack nucleotide homology to PLEs but nonetheless share genomic synteny with PLEs. More generally, our results reveal a previously unknown mechanism deployed by phage parasites to limit packaging of their viral hostsÂ’ genome and highlight the prominent role of nuclease effectors as weapons in the arms race between antagonizing genomes. +::article-doi-list +--- +items: + - 10.1101/2021.07.12.452122 +--- +:: diff --git a/content/2.defense-systems/nlr.md b/content/2.defense-systems/nlr.md index a67939bc21309b61e573cbf42eb5cebafc3323ea..8a2596d355b6ef39f241f077355a8d310c8a20dc 100644 --- a/content/2.defense-systems/nlr.md +++ b/content/2.defense-systems/nlr.md @@ -50,6 +50,10 @@ Subsystem bNACHT09 with a system from \*Escherichia coli\* in \*Escherichia coli ## Relevant abstracts -\*\*Kibby, E. M. et al. Bacterial NLR-related proteins protect against phage. 2022.07.19.500537 Preprint at https://doi.org/10.1101/2022.07.19.500537 (2022).\*\* -Bacteria use a wide range of immune systems to counter phage infection. A subset of these genes share homology with components of eukaryotic immune systems, suggesting that eukaryotes horizontally acquired certain innate immune genes from bacteria. Here we show that proteins containing a NACHT module, the central feature of the animal nucleotide-binding domain and leucine-rich repeat containing gene family (NLRs), are found in bacteria and defend against phages. NACHT proteins are widespread in bacteria, provide immunity against both DNA and RNA phages, and display the characteristic C-terminal sensor, central NACHT, and N-terminal effector modules. Some bacterial NACHT proteins have domain architectures similar to human NLRs that are critical components of inflammasomes. Human disease-associated NLR mutations that cause stimulus-independent activation of the inflammasome also activate bacterial NACHT proteins, supporting a shared signaling mechanism. This work establishes that NACHT module-containing proteins are ancient mediators of innate immunity across the tree of life. +::article-doi-list +--- +items: + - 10.1101/2022.07.19.500537 +--- +:: diff --git a/content/2.defense-systems/olokun.md b/content/2.defense-systems/olokun.md index 7ef105227006d88d91221cd05a72330f67140fac..7ef26b382d49f23d2be482593e06527517f50116 100644 --- a/content/2.defense-systems/olokun.md +++ b/content/2.defense-systems/olokun.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Millman, A. et al. An expanded arsenal of immune systems that protect bacteria from phages. Cell Host Microbe 30, 1556-1569.e5 (2022).\*\* -Bacterial anti-phage systems are frequently clustered in microbial genomes, forming defense islands. This property enabled the recent discovery of multiple defense systems based on their genomic co-localization with known systems, but the full arsenal of anti-phage mechanisms remains unknown. We report the discovery of 21 defense systems that protect bacteria from phages, based on computational genomic analyses and phage-infection experiments. We identified multiple systems with domains involved in eukaryotic antiviral immunity, including those homologous to the ubiquitin-like ISG15 protein, dynamin-like domains, and SEFIR domains, and show their participation in bacterial defenses. Additional systems include domains predicted to manipulate DNA and RNA molecules, alongside toxin-antitoxin systems shown here to function in anti-phage defense. These systems are widely distributed in microbial genomes, and in some bacteria, they form a considerable fraction of the immune arsenal. Our data substantially expand the inventory of defense systems utilized by bacteria to counteract phage infection. +::article-doi-list +--- +items: + - 10.1016/j.chom.2022.09.017 +--- +:: diff --git a/content/2.defense-systems/pago.md b/content/2.defense-systems/pago.md index ce339df75be85c659ccab60f354d245991cd0883..c9dffa181640a112cd04730bd0816000ac52d96d 100644 --- a/content/2.defense-systems/pago.md +++ b/content/2.defense-systems/pago.md @@ -46,21 +46,15 @@ Subsystem SiAgo/Aga1/Aga2 with a system from \*Sulfolobus islandicus\* in \*Sulf ## Relevant abstracts -\*\*Koopal, B. et al. Short prokaryotic Argonaute systems trigger cell death upon detection of invading DNA. Cell 185, 1471-1486.e19 (2022).\*\* -Argonaute proteins use single-stranded RNA or DNA guides to target complementary nucleic acids. This allows eukaryotic Argonaute proteins to mediate RNA interference and long prokaryotic Argonaute proteins to interfere with invading nucleic acids. The function and mechanisms of the phylogenetically distinct short prokaryotic Argonaute proteins remain poorly understood. We demonstrate that short prokaryotic Argonaute and the associated TIR-APAZ (SPARTA) proteins form heterodimeric complexes. Upon guide RNA-mediated target DNA binding, four SPARTA heterodimers form oligomers in which TIR domain-mediated NAD(P)ase activity is unleashed. When expressed in Escherichia coli, SPARTA is activated in the presence of highly transcribed multicopy plasmid DNA, which causes cell death through NAD(P)+ depletion. This results in the removal of plasmid-invaded cells from bacterial cultures. Furthermore, we show that SPARTA can be repurposed for the programmable detection of DNA sequences. In conclusion, our work identifies SPARTA as a prokaryotic immune system that reduces cell viability upon RNA-guided detection of invading DNA. - -\*\*Kuzmenko, A. et al. DNA targeting and interference by a bacterial Argonaute nuclease. Nature 587, 632-637 (2020).\*\* -Members of the conserved Argonaute protein family use small RNA guides to locate their mRNA targets and regulate gene expression and suppress mobile genetic elements in eukaryotes1,2. Argonautes are also present in many bacterial and archaeal species3-5. Unlike eukaryotic proteins, several prokaryotic Argonaute proteins use small DNA guides to cleave DNA, a process known as DNA interference6-10. However, the natural functions and targets of DNA interference are poorly understood, and the mechanisms of DNA guide generation and target discrimination remain unknown. Here we analyse the activity of a bacterial Argonaute nuclease from Clostridium butyricum (CbAgo) in vivo. We show that CbAgo targets multicopy genetic elements and suppresses the propagation of plasmids and infection by phages. CbAgo induces DNA interference between homologous sequences and triggers DNA degradation at double-strand breaks in the target DNA. The loading of CbAgo with locus-specific small DNA guides depends on both its intrinsic endonuclease activity and the cellular double-strand break repair machinery. A similar interaction was reported for the acquisition of new spacers during CRISPR adaptation, and prokaryotic genomes that encode Ago nucleases are enriched in CRISPR-Cas systems. These results identify molecular mechanisms that generate guides for DNA interference and suggest that the recognition of foreign nucleic acids by prokaryotic defence systems involves common principles. - -\*\*Makarova, K. S., Wolf, Y. I., van der Oost, J. & Koonin, E. V. Prokaryotic homologs of Argonaute proteins are predicted to function as key components of a novel system of defense against mobile genetic elements. Biol Direct 4, 29 (2009).\*\* -BACKGROUND: In eukaryotes, RNA interference (RNAi) is a major mechanism of defense against viruses and transposable elements as well of regulating translation of endogenous mRNAs. The RNAi systems recognize the target RNA molecules via small guide RNAs that are completely or partially complementary to a region of the target. Key components of the RNAi systems are proteins of the Argonaute-PIWI family some of which function as slicers, the nucleases that cleave the target RNA that is base-paired to a guide RNA. Numerous prokaryotes possess the CRISPR-associated system (CASS) of defense against phages and plasmids that is, in part, mechanistically analogous but not homologous to eukaryotic RNAi systems. Many prokaryotes also encode homologs of Argonaute-PIWI proteins but their functions remain unknown. RESULTS: We present a detailed analysis of Argonaute-PIWI protein sequences and the genomic neighborhoods of the respective genes in prokaryotes. Whereas eukaryotic Ago/PIWI proteins always contain PAZ (oligonucleotide binding) and PIWI (active or inactivated nuclease) domains, the prokaryotic Argonaute homologs (pAgos) fall into two major groups in which the PAZ domain is either present or absent. The monophyly of each group is supported by a phylogenetic analysis of the conserved PIWI-domains. Almost all pAgos that lack a PAZ domain appear to be inactivated, and the respective genes are associated with a variety of predicted nucleases in putative operons. An additional, uncharacterized domain that is fused to various nucleases appears to be a unique signature of operons encoding the short (lacking PAZ) pAgo form. By contrast, almost all PAZ-domain containing pAgos are predicted to be active nucleases. Some proteins of this group (e.g., that from Aquifex aeolicus) have been experimentally shown to possess nuclease activity, and are not typically associated with genes for other (putative) nucleases. Given these observations, the apparent extensive horizontal transfer of pAgo genes, and their common, statistically significant over-representation in genomic neighborhoods enriched in genes encoding proteins involved in the defense against phages and/or plasmids, we hypothesize that pAgos are key components of a novel class of defense systems. The PAZ-domain containing pAgos are predicted to directly destroy virus or plasmid nucleic acids via their nuclease activity, whereas the apparently inactivated, PAZ-lacking pAgos could be structural subunits of protein complexes that contain, as active moieties, the putative nucleases that we predict to be co-expressed with these pAgos. All these nucleases are predicted to be DNA endonucleases, so it seems most probable that the putative novel phage/plasmid-defense system targets phage DNA rather than mRNAs. Given that in eukaryotic RNAi systems, the PAZ domain binds a guide RNA and positions it on the complementary region of the target, we further speculate that pAgos function on a similar principle (the guide being either DNA or RNA), and that the uncharacterized domain found in putative operons with the short forms of pAgos is a functional substitute for the PAZ domain. CONCLUSION: The hypothesis that pAgos are key components of a novel prokaryotic immune system that employs guide RNA or DNA molecules to degrade nucleic acids of invading mobile elements implies a functional analogy with the prokaryotic CASS and a direct evolutionary connection with eukaryotic RNAi. The predictions of the hypothesis including both the activities of pAgos and those of the associated endonucleases are readily amenable to experimental tests. - -\*\*Zeng, Z. et al. A short prokaryotic Argonaute activates membrane effector to confer antiviral defense. Cell Host Microbe 30, 930-943.e6 (2022).\*\* -Argonaute (Ago) proteins are widespread nucleic-acid-guided enzymes that recognize targets through complementary base pairing. Although, in eukaryotes, Agos are involved in RNA silencing, the functions of prokaryotic Agos (pAgos) remain largely unknown. In particular, a clade of truncated and catalytically inactive pAgos (short pAgos) lacks characterization. Here, we reveal that a short pAgo protein in the archaeon Sulfolobus islandicus, together with its two genetically associated proteins, Aga1 and Aga2, provide robust antiviral protection via abortive infection. Aga2 is a toxic transmembrane effector that binds anionic phospholipids via a basic pocket, resulting in membrane depolarization and cell killing. Ago and Aga1 form a stable complex that exhibits nucleic-acid-directed nucleic-acid-recognition ability and directly interacts with Aga2, pointing to an immune sensing mechanism. Together, our results highlight the cooperation between pAgos and their widespread associated proteins, suggesting an uncharted diversity of pAgo-derived immune systems. - -\*\*.Garb, J. et al. Multiple phage resistance systems inhibit infection via SIR2-dependent NAD+ depletion. Nat Microbiol 7, 1849-1856 (2022).\*\* -Defence-associated sirtuins (DSRs) comprise a family of proteins that defend bacteria from phage infection via an unknown mechanism. These proteins are common in bacteria and harbour an N-terminal sirtuin (SIR2) domain. In this study we report that DSR proteins degrade nicotinamide adenine dinucleotide (NAD+) during infection, depleting the cell of this essential molecule and aborting phage propagation. Our data show that one of these proteins, DSR2, directly identifies phage tail tube proteins and then becomes an active NADase in Bacillus subtilis. Using a phage mating methodology that promotes genetic exchange between pairs of DSR2-sensitive and DSR2-resistant phages, we further show that some phages express anti-DSR2 proteins that bind and repress DSR2. Finally, we demonstrate that the SIR2 domain serves as an effector NADase in a diverse set of phage defence systems outside the DSR family. Our results establish the general role of SIR2 domains in bacterial immunity against phages. - -\*\*Zaremba, M. et al. Short prokaryotic Argonautes provide defence against incoming mobile genetic elements through NAD+ depletion. Nat Microbiol 7, 1857-1869 (2022).\*\* -Argonaute (Ago) proteins are found in all three domains of life. The so-called long Agos are composed of four major domains (N, PAZ, MID and PIWI) and contribute to RNA silencing in eukaryotes (eAgos) or defence against invading mobile genetic elements in prokaryotes (pAgos). The majority (~60%) of pAgos identified bioinformatically are shorter (comprising only MID and PIWI domains) and are typically associated with Sir2, Mrr or TIR domain-containing proteins. The cellular function and mechanism of short pAgos remain enigmatic. Here we show that Geobacter sulfurreducens short pAgo and the NAD+-bound Sir2 protein form a stable heterodimeric complex. The GsSir2/Ago complex presumably recognizes invading plasmid or phage DNA and activates the Sir2 subunit, which triggers endogenous NAD+ depletion and cell death, and prevents the propagation of invading DNA. We reconstituted NAD+ depletion activity in vitro and showed that activated GsSir2/Ago complex functions as a NADase that hydrolyses NAD+ to ADPR. Thus, short Sir2-associated pAgos provide defence against phages and plasmids, underscoring the diversity of mechanisms of prokaryotic Agos. +::article-doi-list +--- +items: + - 10.1016/j.cell.2022.03.012 + - 10.1016/j.chom.2022.04.015 + - 10.1038/s41564-022-01207-8 + - 10.1038/s41586-020-2605-1 + - 10.1186/1745-6150-4-29 + - 10.1038/s41564-022-01239-0 +--- +:: diff --git a/content/2.defense-systems/pd-lambda-1.md b/content/2.defense-systems/pd-lambda-1.md index 357b423b948d88abe3a365ff2288b2d3d8271890..823c9d05c8e920764a7bce4e9927f9ca3939323e 100644 --- a/content/2.defense-systems/pd-lambda-1.md +++ b/content/2.defense-systems/pd-lambda-1.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Vassallo, C. N., Doering, C. R., Littlehale, M. L., Teodoro, G. I. C. & Laub, M. T. A functional selection reveals previously undetected anti-phage defence systems in the E. coli pangenome. Nat Microbiol 7, 1568-1579 (2022).\*\* -The ancient, ongoing coevolutionary battle between bacteria and their viruses, bacteriophages, has given rise to sophisticated immune systems including restriction-modification and CRISPR-Cas. Many additional anti-phage systems have been identified using computational approaches based on genomic co-location within defence islands, but these screens may not be exhaustive. Here we developed an experimental selection scheme agnostic to genomic context to identify defence systems in 71 diverse E. coli strains. Our results unveil 21 conserved defence systems, none of which were previously detected as enriched in defence islands. Additionally, our work indicates that intact prophages and mobile genetic elements are primary reservoirs and distributors of defence systems in E. coli, with defence systems typically carried in specific locations or hotspots. These hotspots encode dozens of additional uncharacterized defence system candidates. Our findings reveal an extended landscape of antiviral immunity in E. coli and provide an approach for mapping defence systems in other species. +::article-doi-list +--- +items: + - 10.1038/s41564-022-01219-4 +--- +:: diff --git a/content/2.defense-systems/pd-lambda-2.md b/content/2.defense-systems/pd-lambda-2.md index adb7c4b4cf44d2fbd29414a16fc5f08c944668b7..514e03ba075739d9d0328245620c0f2c1e932b94 100644 --- a/content/2.defense-systems/pd-lambda-2.md +++ b/content/2.defense-systems/pd-lambda-2.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Vassallo, C. N., Doering, C. R., Littlehale, M. L., Teodoro, G. I. C. & Laub, M. T. A functional selection reveals previously undetected anti-phage defence systems in the E. coli pangenome. Nat Microbiol 7, 1568-1579 (2022).\*\* -The ancient, ongoing coevolutionary battle between bacteria and their viruses, bacteriophages, has given rise to sophisticated immune systems including restriction-modification and CRISPR-Cas. Many additional anti-phage systems have been identified using computational approaches based on genomic co-location within defence islands, but these screens may not be exhaustive. Here we developed an experimental selection scheme agnostic to genomic context to identify defence systems in 71 diverse E. coli strains. Our results unveil 21 conserved defence systems, none of which were previously detected as enriched in defence islands. Additionally, our work indicates that intact prophages and mobile genetic elements are primary reservoirs and distributors of defence systems in E. coli, with defence systems typically carried in specific locations or hotspots. These hotspots encode dozens of additional uncharacterized defence system candidates. Our findings reveal an extended landscape of antiviral immunity in E. coli and provide an approach for mapping defence systems in other species. +::article-doi-list +--- +items: + - 10.1038/s41564-022-01219-4 +--- +:: diff --git a/content/2.defense-systems/pd-lambda-3.md b/content/2.defense-systems/pd-lambda-3.md index 8867540ad5f825ce5d63c737c0635e9e6d38baf1..23c5735e4f446663862ab8c08840c8ffc0a06542 100644 --- a/content/2.defense-systems/pd-lambda-3.md +++ b/content/2.defense-systems/pd-lambda-3.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Vassallo, C. N., Doering, C. R., Littlehale, M. L., Teodoro, G. I. C. & Laub, M. T. A functional selection reveals previously undetected anti-phage defence systems in the E. coli pangenome. Nat Microbiol 7, 1568-1579 (2022).\*\* -The ancient, ongoing coevolutionary battle between bacteria and their viruses, bacteriophages, has given rise to sophisticated immune systems including restriction-modification and CRISPR-Cas. Many additional anti-phage systems have been identified using computational approaches based on genomic co-location within defence islands, but these screens may not be exhaustive. Here we developed an experimental selection scheme agnostic to genomic context to identify defence systems in 71 diverse E. coli strains. Our results unveil 21 conserved defence systems, none of which were previously detected as enriched in defence islands. Additionally, our work indicates that intact prophages and mobile genetic elements are primary reservoirs and distributors of defence systems in E. coli, with defence systems typically carried in specific locations or hotspots. These hotspots encode dozens of additional uncharacterized defence system candidates. Our findings reveal an extended landscape of antiviral immunity in E. coli and provide an approach for mapping defence systems in other species. +::article-doi-list +--- +items: + - 10.1038/s41564-022-01219-4 +--- +:: diff --git a/content/2.defense-systems/pd-lambda-4.md b/content/2.defense-systems/pd-lambda-4.md index 6fb9934319b76adf90793491c1bf61fd19cc2464..caea84c1c715e19650c3fcaa9a6a12514b0d6600 100644 --- a/content/2.defense-systems/pd-lambda-4.md +++ b/content/2.defense-systems/pd-lambda-4.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Vassallo, C. N., Doering, C. R., Littlehale, M. L., Teodoro, G. I. C. & Laub, M. T. A functional selection reveals previously undetected anti-phage defence systems in the E. coli pangenome. Nat Microbiol 7, 1568-1579 (2022).\*\* -The ancient, ongoing coevolutionary battle between bacteria and their viruses, bacteriophages, has given rise to sophisticated immune systems including restriction-modification and CRISPR-Cas. Many additional anti-phage systems have been identified using computational approaches based on genomic co-location within defence islands, but these screens may not be exhaustive. Here we developed an experimental selection scheme agnostic to genomic context to identify defence systems in 71 diverse E. coli strains. Our results unveil 21 conserved defence systems, none of which were previously detected as enriched in defence islands. Additionally, our work indicates that intact prophages and mobile genetic elements are primary reservoirs and distributors of defence systems in E. coli, with defence systems typically carried in specific locations or hotspots. These hotspots encode dozens of additional uncharacterized defence system candidates. Our findings reveal an extended landscape of antiviral immunity in E. coli and provide an approach for mapping defence systems in other species. +::article-doi-list +--- +items: + - 10.1038/s41564-022-01219-4 +--- +:: diff --git a/content/2.defense-systems/pd-lambda-5.md b/content/2.defense-systems/pd-lambda-5.md index e44331b94159466c9f4e15f3dd476e2e6e8cc773..1ff6bd292223043abafea089e7a7a94aa9139d0c 100644 --- a/content/2.defense-systems/pd-lambda-5.md +++ b/content/2.defense-systems/pd-lambda-5.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Vassallo, C. N., Doering, C. R., Littlehale, M. L., Teodoro, G. I. C. & Laub, M. T. A functional selection reveals previously undetected anti-phage defence systems in the E. coli pangenome. Nat Microbiol 7, 1568-1579 (2022).\*\* -The ancient, ongoing coevolutionary battle between bacteria and their viruses, bacteriophages, has given rise to sophisticated immune systems including restriction-modification and CRISPR-Cas. Many additional anti-phage systems have been identified using computational approaches based on genomic co-location within defence islands, but these screens may not be exhaustive. Here we developed an experimental selection scheme agnostic to genomic context to identify defence systems in 71 diverse E. coli strains. Our results unveil 21 conserved defence systems, none of which were previously detected as enriched in defence islands. Additionally, our work indicates that intact prophages and mobile genetic elements are primary reservoirs and distributors of defence systems in E. coli, with defence systems typically carried in specific locations or hotspots. These hotspots encode dozens of additional uncharacterized defence system candidates. Our findings reveal an extended landscape of antiviral immunity in E. coli and provide an approach for mapping defence systems in other species. +::article-doi-list +--- +items: + - 10.1038/s41564-022-01219-4 +--- +:: diff --git a/content/2.defense-systems/pd-lambda-6.md b/content/2.defense-systems/pd-lambda-6.md index b31b5406bbb1fee742110faf1c73daa2fbded749..797d8817c9613adb0137beb6cd77ba4734988c30 100644 --- a/content/2.defense-systems/pd-lambda-6.md +++ b/content/2.defense-systems/pd-lambda-6.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Vassallo, C. N., Doering, C. R., Littlehale, M. L., Teodoro, G. I. C. & Laub, M. T. A functional selection reveals previously undetected anti-phage defence systems in the E. coli pangenome. Nat Microbiol 7, 1568-1579 (2022).\*\* -The ancient, ongoing coevolutionary battle between bacteria and their viruses, bacteriophages, has given rise to sophisticated immune systems including restriction-modification and CRISPR-Cas. Many additional anti-phage systems have been identified using computational approaches based on genomic co-location within defence islands, but these screens may not be exhaustive. Here we developed an experimental selection scheme agnostic to genomic context to identify defence systems in 71 diverse E. coli strains. Our results unveil 21 conserved defence systems, none of which were previously detected as enriched in defence islands. Additionally, our work indicates that intact prophages and mobile genetic elements are primary reservoirs and distributors of defence systems in E. coli, with defence systems typically carried in specific locations or hotspots. These hotspots encode dozens of additional uncharacterized defence system candidates. Our findings reveal an extended landscape of antiviral immunity in E. coli and provide an approach for mapping defence systems in other species. +::article-doi-list +--- +items: + - 10.1038/s41564-022-01219-4 +--- +:: diff --git a/content/2.defense-systems/pd-t4-1.md b/content/2.defense-systems/pd-t4-1.md index 84fff571ea8394b55d53b07a2944bfa9d8afd652..1e25c4d273a12bfb167610fe517079a015cc25ca 100644 --- a/content/2.defense-systems/pd-t4-1.md +++ b/content/2.defense-systems/pd-t4-1.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Johnson, C. M., Harden, M. M. & Grossman, A. D. Interactions between mobile genetic elements: An anti-phage gene in an integrative and conjugative element protects host cells from predation by a temperate bacteriophage. PLOS Genetics 18, e1010065 (2022).\*\* -Most bacterial genomes contain horizontally acquired and transmissible mobile genetic elements, including temperate bacteriophages and integrative and conjugative elements. Little is known about how these elements interact and co-evolved as parts of their host genomes. In many cases, it is not known what advantages, if any, these elements provide to their bacterial hosts. Most strains of Bacillus subtilis contain the temperate phage SPß and the integrative and conjugative element ICEBs1. Here we show that the presence of ICEBs1 in cells protects populations of B. subtilis from predation by SPß, likely providing selective pressure for the maintenance of ICEBs1 in B. subtilis. A single gene in ICEBs1 (yddK, now called spbK for SPß killing) was both necessary and sufficient for this protection. spbK inhibited production of SPß, during both activation of a lysogen and following de novo infection. We found that expression spbK, together with the SPß gene yonE constitutes an abortive infection system that leads to cell death. spbK encodes a TIR (Toll-interleukin-1 receptor)-domain protein with similarity to some plant antiviral proteins and animal innate immune signaling proteins. We postulate that many uncharacterized cargo genes in ICEs may confer selective advantage to cells by protecting against other mobile elements. +::article-doi-list +--- +items: + - 10.1371/journal.pgen.1010065 +--- +:: diff --git a/content/2.defense-systems/pd-t4-10.md b/content/2.defense-systems/pd-t4-10.md index a9dd4ceae6840744ee26d320c745ee02cadf274c..971077799c2f85210d189d7e5affcb64e0dbae1a 100644 --- a/content/2.defense-systems/pd-t4-10.md +++ b/content/2.defense-systems/pd-t4-10.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Johnson, C. M., Harden, M. M. & Grossman, A. D. Interactions between mobile genetic elements: An anti-phage gene in an integrative and conjugative element protects host cells from predation by a temperate bacteriophage. PLOS Genetics 18, e1010065 (2022).\*\* -Most bacterial genomes contain horizontally acquired and transmissible mobile genetic elements, including temperate bacteriophages and integrative and conjugative elements. Little is known about how these elements interact and co-evolved as parts of their host genomes. In many cases, it is not known what advantages, if any, these elements provide to their bacterial hosts. Most strains of Bacillus subtilis contain the temperate phage SPß and the integrative and conjugative element ICEBs1. Here we show that the presence of ICEBs1 in cells protects populations of B. subtilis from predation by SPß, likely providing selective pressure for the maintenance of ICEBs1 in B. subtilis. A single gene in ICEBs1 (yddK, now called spbK for SPß killing) was both necessary and sufficient for this protection. spbK inhibited production of SPß, during both activation of a lysogen and following de novo infection. We found that expression spbK, together with the SPß gene yonE constitutes an abortive infection system that leads to cell death. spbK encodes a TIR (Toll-interleukin-1 receptor)-domain protein with similarity to some plant antiviral proteins and animal innate immune signaling proteins. We postulate that many uncharacterized cargo genes in ICEs may confer selective advantage to cells by protecting against other mobile elements. +::article-doi-list +--- +items: + - 10.1371/journal.pgen.1010065 +--- +:: diff --git a/content/2.defense-systems/pd-t4-2.md b/content/2.defense-systems/pd-t4-2.md index 5719c580d81f7bec826b8b2dd1494a71fb44448d..51ff20ad87ec7bd2cf5661ad7aa2aa9a6043564d 100644 --- a/content/2.defense-systems/pd-t4-2.md +++ b/content/2.defense-systems/pd-t4-2.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Vassallo, C. N., Doering, C. R., Littlehale, M. L., Teodoro, G. I. C. & Laub, M. T. A functional selection reveals previously undetected anti-phage defence systems in the E. coli pangenome. Nat Microbiol 7, 1568-1579 (2022).\*\* -The ancient, ongoing coevolutionary battle between bacteria and their viruses, bacteriophages, has given rise to sophisticated immune systems including restriction-modification and CRISPR-Cas. Many additional anti-phage systems have been identified using computational approaches based on genomic co-location within defence islands, but these screens may not be exhaustive. Here we developed an experimental selection scheme agnostic to genomic context to identify defence systems in 71 diverse E. coli strains. Our results unveil 21 conserved defence systems, none of which were previously detected as enriched in defence islands. Additionally, our work indicates that intact prophages and mobile genetic elements are primary reservoirs and distributors of defence systems in E. coli, with defence systems typically carried in specific locations or hotspots. These hotspots encode dozens of additional uncharacterized defence system candidates. Our findings reveal an extended landscape of antiviral immunity in E. coli and provide an approach for mapping defence systems in other species. +::article-doi-list +--- +items: + - 10.1038/s41564-022-01219-4 +--- +:: diff --git a/content/2.defense-systems/pd-t4-3.md b/content/2.defense-systems/pd-t4-3.md index 3011a64583f1f76d9b6b7bf232baedd8c216523d..d374dd097eb425b0bdcda32c219b6c348740a1c1 100644 --- a/content/2.defense-systems/pd-t4-3.md +++ b/content/2.defense-systems/pd-t4-3.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Vassallo, C. N., Doering, C. R., Littlehale, M. L., Teodoro, G. I. C. & Laub, M. T. A functional selection reveals previously undetected anti-phage defence systems in the E. coli pangenome. Nat Microbiol 7, 1568-1579 (2022).\*\* -The ancient, ongoing coevolutionary battle between bacteria and their viruses, bacteriophages, has given rise to sophisticated immune systems including restriction-modification and CRISPR-Cas. Many additional anti-phage systems have been identified using computational approaches based on genomic co-location within defence islands, but these screens may not be exhaustive. Here we developed an experimental selection scheme agnostic to genomic context to identify defence systems in 71 diverse E. coli strains. Our results unveil 21 conserved defence systems, none of which were previously detected as enriched in defence islands. Additionally, our work indicates that intact prophages and mobile genetic elements are primary reservoirs and distributors of defence systems in E. coli, with defence systems typically carried in specific locations or hotspots. These hotspots encode dozens of additional uncharacterized defence system candidates. Our findings reveal an extended landscape of antiviral immunity in E. coli and provide an approach for mapping defence systems in other species. +::article-doi-list +--- +items: + - 10.1038/s41564-022-01219-4 +--- +:: diff --git a/content/2.defense-systems/pd-t4-4.md b/content/2.defense-systems/pd-t4-4.md index 4a42a0ca50067d6d539a0483c536ea94a6d631bd..68a83f0ac74fe8439ff1d8fa209a239c5fc1c56d 100644 --- a/content/2.defense-systems/pd-t4-4.md +++ b/content/2.defense-systems/pd-t4-4.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Vassallo, C. N., Doering, C. R., Littlehale, M. L., Teodoro, G. I. C. & Laub, M. T. A functional selection reveals previously undetected anti-phage defence systems in the E. coli pangenome. Nat Microbiol 7, 1568-1579 (2022).\*\* -The ancient, ongoing coevolutionary battle between bacteria and their viruses, bacteriophages, has given rise to sophisticated immune systems including restriction-modification and CRISPR-Cas. Many additional anti-phage systems have been identified using computational approaches based on genomic co-location within defence islands, but these screens may not be exhaustive. Here we developed an experimental selection scheme agnostic to genomic context to identify defence systems in 71 diverse E. coli strains. Our results unveil 21 conserved defence systems, none of which were previously detected as enriched in defence islands. Additionally, our work indicates that intact prophages and mobile genetic elements are primary reservoirs and distributors of defence systems in E. coli, with defence systems typically carried in specific locations or hotspots. These hotspots encode dozens of additional uncharacterized defence system candidates. Our findings reveal an extended landscape of antiviral immunity in E. coli and provide an approach for mapping defence systems in other species. +::article-doi-list +--- +items: + - 10.1038/s41564-022-01219-4 +--- +:: diff --git a/content/2.defense-systems/pd-t4-5.md b/content/2.defense-systems/pd-t4-5.md index d1e1757bedbeac07cb520ca8d28b1595e36ce706..d3b03c615e1f6f985739d582346deeaa34098e8e 100644 --- a/content/2.defense-systems/pd-t4-5.md +++ b/content/2.defense-systems/pd-t4-5.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Vassallo, C. N., Doering, C. R., Littlehale, M. L., Teodoro, G. I. C. & Laub, M. T. A functional selection reveals previously undetected anti-phage defence systems in the E. coli pangenome. Nat Microbiol 7, 1568-1579 (2022).\*\* -The ancient, ongoing coevolutionary battle between bacteria and their viruses, bacteriophages, has given rise to sophisticated immune systems including restriction-modification and CRISPR-Cas. Many additional anti-phage systems have been identified using computational approaches based on genomic co-location within defence islands, but these screens may not be exhaustive. Here we developed an experimental selection scheme agnostic to genomic context to identify defence systems in 71 diverse E. coli strains. Our results unveil 21 conserved defence systems, none of which were previously detected as enriched in defence islands. Additionally, our work indicates that intact prophages and mobile genetic elements are primary reservoirs and distributors of defence systems in E. coli, with defence systems typically carried in specific locations or hotspots. These hotspots encode dozens of additional uncharacterized defence system candidates. Our findings reveal an extended landscape of antiviral immunity in E. coli and provide an approach for mapping defence systems in other species. +::article-doi-list +--- +items: + - 10.1038/s41564-022-01219-4 +--- +:: diff --git a/content/2.defense-systems/pd-t4-6.md b/content/2.defense-systems/pd-t4-6.md index 140fa426c35b0c54a20aaebc62a2a387af39b6ed..59d05aa1ce611be8d97ef109b3bf4afd682bd3d9 100644 --- a/content/2.defense-systems/pd-t4-6.md +++ b/content/2.defense-systems/pd-t4-6.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Vassallo, C. N., Doering, C. R., Littlehale, M. L., Teodoro, G. I. C. & Laub, M. T. A functional selection reveals previously undetected anti-phage defence systems in the E. coli pangenome. Nat Microbiol 7, 1568-1579 (2022).\*\* -The ancient, ongoing coevolutionary battle between bacteria and their viruses, bacteriophages, has given rise to sophisticated immune systems including restriction-modification and CRISPR-Cas. Many additional anti-phage systems have been identified using computational approaches based on genomic co-location within defence islands, but these screens may not be exhaustive. Here we developed an experimental selection scheme agnostic to genomic context to identify defence systems in 71 diverse E. coli strains. Our results unveil 21 conserved defence systems, none of which were previously detected as enriched in defence islands. Additionally, our work indicates that intact prophages and mobile genetic elements are primary reservoirs and distributors of defence systems in E. coli, with defence systems typically carried in specific locations or hotspots. These hotspots encode dozens of additional uncharacterized defence system candidates. Our findings reveal an extended landscape of antiviral immunity in E. coli and provide an approach for mapping defence systems in other species. +::article-doi-list +--- +items: + - 10.1038/s41564-022-01219-4 +--- +:: diff --git a/content/2.defense-systems/pd-t4-7.md b/content/2.defense-systems/pd-t4-7.md index a8a92fa52bd62321cafa4c73e19591d3b2066dec..39e5cb8f3a4dd1309fafbe677017071d80a3499e 100644 --- a/content/2.defense-systems/pd-t4-7.md +++ b/content/2.defense-systems/pd-t4-7.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Vassallo, C. N., Doering, C. R., Littlehale, M. L., Teodoro, G. I. C. & Laub, M. T. A functional selection reveals previously undetected anti-phage defence systems in the E. coli pangenome. Nat Microbiol 7, 1568-1579 (2022).\*\* -The ancient, ongoing coevolutionary battle between bacteria and their viruses, bacteriophages, has given rise to sophisticated immune systems including restriction-modification and CRISPR-Cas. Many additional anti-phage systems have been identified using computational approaches based on genomic co-location within defence islands, but these screens may not be exhaustive. Here we developed an experimental selection scheme agnostic to genomic context to identify defence systems in 71 diverse E. coli strains. Our results unveil 21 conserved defence systems, none of which were previously detected as enriched in defence islands. Additionally, our work indicates that intact prophages and mobile genetic elements are primary reservoirs and distributors of defence systems in E. coli, with defence systems typically carried in specific locations or hotspots. These hotspots encode dozens of additional uncharacterized defence system candidates. Our findings reveal an extended landscape of antiviral immunity in E. coli and provide an approach for mapping defence systems in other species. +::article-doi-list +--- +items: + - 10.1038/s41564-022-01219-4 +--- +:: diff --git a/content/2.defense-systems/pd-t4-8.md b/content/2.defense-systems/pd-t4-8.md index 15b657045cc7c4eb50903bffa6da94936cdc9872..eff2409944b881ea8aa79ceed286430a9c815d42 100644 --- a/content/2.defense-systems/pd-t4-8.md +++ b/content/2.defense-systems/pd-t4-8.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Vassallo, C. N., Doering, C. R., Littlehale, M. L., Teodoro, G. I. C. & Laub, M. T. A functional selection reveals previously undetected anti-phage defence systems in the E. coli pangenome. Nat Microbiol 7, 1568-1579 (2022).\*\* -The ancient, ongoing coevolutionary battle between bacteria and their viruses, bacteriophages, has given rise to sophisticated immune systems including restriction-modification and CRISPR-Cas. Many additional anti-phage systems have been identified using computational approaches based on genomic co-location within defence islands, but these screens may not be exhaustive. Here we developed an experimental selection scheme agnostic to genomic context to identify defence systems in 71 diverse E. coli strains. Our results unveil 21 conserved defence systems, none of which were previously detected as enriched in defence islands. Additionally, our work indicates that intact prophages and mobile genetic elements are primary reservoirs and distributors of defence systems in E. coli, with defence systems typically carried in specific locations or hotspots. These hotspots encode dozens of additional uncharacterized defence system candidates. Our findings reveal an extended landscape of antiviral immunity in E. coli and provide an approach for mapping defence systems in other species. +::article-doi-list +--- +items: + - 10.1038/s41564-022-01219-4 +--- +:: diff --git a/content/2.defense-systems/pd-t4-9.md b/content/2.defense-systems/pd-t4-9.md index 71ec50923546588d08b36bb1fa35ebbc980e2fc7..475c805d7cdec9429763898d17f1e0f068c60489 100644 --- a/content/2.defense-systems/pd-t4-9.md +++ b/content/2.defense-systems/pd-t4-9.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Vassallo, C. N., Doering, C. R., Littlehale, M. L., Teodoro, G. I. C. & Laub, M. T. A functional selection reveals previously undetected anti-phage defence systems in the E. coli pangenome. Nat Microbiol 7, 1568-1579 (2022).\*\* -The ancient, ongoing coevolutionary battle between bacteria and their viruses, bacteriophages, has given rise to sophisticated immune systems including restriction-modification and CRISPR-Cas. Many additional anti-phage systems have been identified using computational approaches based on genomic co-location within defence islands, but these screens may not be exhaustive. Here we developed an experimental selection scheme agnostic to genomic context to identify defence systems in 71 diverse E. coli strains. Our results unveil 21 conserved defence systems, none of which were previously detected as enriched in defence islands. Additionally, our work indicates that intact prophages and mobile genetic elements are primary reservoirs and distributors of defence systems in E. coli, with defence systems typically carried in specific locations or hotspots. These hotspots encode dozens of additional uncharacterized defence system candidates. Our findings reveal an extended landscape of antiviral immunity in E. coli and provide an approach for mapping defence systems in other species. +::article-doi-list +--- +items: + - 10.1038/s41564-022-01219-4 +--- +:: diff --git a/content/2.defense-systems/pd-t7-1.md b/content/2.defense-systems/pd-t7-1.md index e495e428701a7eeaedc301076bd2de1e5516ea41..5acbdaac4ea886fcf91957d6331cfd2cc9fc5099 100644 --- a/content/2.defense-systems/pd-t7-1.md +++ b/content/2.defense-systems/pd-t7-1.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Vassallo, C. N., Doering, C. R., Littlehale, M. L., Teodoro, G. I. C. & Laub, M. T. A functional selection reveals previously undetected anti-phage defence systems in the E. coli pangenome. Nat Microbiol 7, 1568-1579 (2022).\*\* -The ancient, ongoing coevolutionary battle between bacteria and their viruses, bacteriophages, has given rise to sophisticated immune systems including restriction-modification and CRISPR-Cas. Many additional anti-phage systems have been identified using computational approaches based on genomic co-location within defence islands, but these screens may not be exhaustive. Here we developed an experimental selection scheme agnostic to genomic context to identify defence systems in 71 diverse E. coli strains. Our results unveil 21 conserved defence systems, none of which were previously detected as enriched in defence islands. Additionally, our work indicates that intact prophages and mobile genetic elements are primary reservoirs and distributors of defence systems in E. coli, with defence systems typically carried in specific locations or hotspots. These hotspots encode dozens of additional uncharacterized defence system candidates. Our findings reveal an extended landscape of antiviral immunity in E. coli and provide an approach for mapping defence systems in other species. +::article-doi-list +--- +items: + - 10.1038/s41564-022-01219-4 +--- +:: diff --git a/content/2.defense-systems/pd-t7-2.md b/content/2.defense-systems/pd-t7-2.md index 85cce53e6d6c24fa3e051b71c875d3e76b9d56c3..c41d865fd9e94a7b08a9760f28c8d0670d439fbc 100644 --- a/content/2.defense-systems/pd-t7-2.md +++ b/content/2.defense-systems/pd-t7-2.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Vassallo, C. N., Doering, C. R., Littlehale, M. L., Teodoro, G. I. C. & Laub, M. T. A functional selection reveals previously undetected anti-phage defence systems in the E. coli pangenome. Nat Microbiol 7, 1568-1579 (2022).\*\* -The ancient, ongoing coevolutionary battle between bacteria and their viruses, bacteriophages, has given rise to sophisticated immune systems including restriction-modification and CRISPR-Cas. Many additional anti-phage systems have been identified using computational approaches based on genomic co-location within defence islands, but these screens may not be exhaustive. Here we developed an experimental selection scheme agnostic to genomic context to identify defence systems in 71 diverse E. coli strains. Our results unveil 21 conserved defence systems, none of which were previously detected as enriched in defence islands. Additionally, our work indicates that intact prophages and mobile genetic elements are primary reservoirs and distributors of defence systems in E. coli, with defence systems typically carried in specific locations or hotspots. These hotspots encode dozens of additional uncharacterized defence system candidates. Our findings reveal an extended landscape of antiviral immunity in E. coli and provide an approach for mapping defence systems in other species. +::article-doi-list +--- +items: + - 10.1038/s41564-022-01219-4 +--- +:: diff --git a/content/2.defense-systems/pd-t7-3.md b/content/2.defense-systems/pd-t7-3.md index 6cb9f2f08e42638236adf2dad5ff1eee8f82b174..254a02f4ce6368d1ac45c96c23be8985553a65fb 100644 --- a/content/2.defense-systems/pd-t7-3.md +++ b/content/2.defense-systems/pd-t7-3.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Vassallo, C. N., Doering, C. R., Littlehale, M. L., Teodoro, G. I. C. & Laub, M. T. A functional selection reveals previously undetected anti-phage defence systems in the E. coli pangenome. Nat Microbiol 7, 1568-1579 (2022).\*\* -The ancient, ongoing coevolutionary battle between bacteria and their viruses, bacteriophages, has given rise to sophisticated immune systems including restriction-modification and CRISPR-Cas. Many additional anti-phage systems have been identified using computational approaches based on genomic co-location within defence islands, but these screens may not be exhaustive. Here we developed an experimental selection scheme agnostic to genomic context to identify defence systems in 71 diverse E. coli strains. Our results unveil 21 conserved defence systems, none of which were previously detected as enriched in defence islands. Additionally, our work indicates that intact prophages and mobile genetic elements are primary reservoirs and distributors of defence systems in E. coli, with defence systems typically carried in specific locations or hotspots. These hotspots encode dozens of additional uncharacterized defence system candidates. Our findings reveal an extended landscape of antiviral immunity in E. coli and provide an approach for mapping defence systems in other species. +::article-doi-list +--- +items: + - 10.1038/s41564-022-01219-4 +--- +:: diff --git a/content/2.defense-systems/pd-t7-4.md b/content/2.defense-systems/pd-t7-4.md index 673b2824f1a0ba9c7351b9b6d6231bbe3516a1c3..2e5e95bf48029e0356ecd6e8b33560281566f48d 100644 --- a/content/2.defense-systems/pd-t7-4.md +++ b/content/2.defense-systems/pd-t7-4.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Vassallo, C. N., Doering, C. R., Littlehale, M. L., Teodoro, G. I. C. & Laub, M. T. A functional selection reveals previously undetected anti-phage defence systems in the E. coli pangenome. Nat Microbiol 7, 1568-1579 (2022).\*\* -The ancient, ongoing coevolutionary battle between bacteria and their viruses, bacteriophages, has given rise to sophisticated immune systems including restriction-modification and CRISPR-Cas. Many additional anti-phage systems have been identified using computational approaches based on genomic co-location within defence islands, but these screens may not be exhaustive. Here we developed an experimental selection scheme agnostic to genomic context to identify defence systems in 71 diverse E. coli strains. Our results unveil 21 conserved defence systems, none of which were previously detected as enriched in defence islands. Additionally, our work indicates that intact prophages and mobile genetic elements are primary reservoirs and distributors of defence systems in E. coli, with defence systems typically carried in specific locations or hotspots. These hotspots encode dozens of additional uncharacterized defence system candidates. Our findings reveal an extended landscape of antiviral immunity in E. coli and provide an approach for mapping defence systems in other species. +::article-doi-list +--- +items: + - 10.1038/s41564-022-01219-4 +--- +:: diff --git a/content/2.defense-systems/pd-t7-5.md b/content/2.defense-systems/pd-t7-5.md index 49af4ee267a889cc845b0efd6b765316c26d3998..ba06272312f5d5710d663635ff7d6e9aa40f0eb3 100644 --- a/content/2.defense-systems/pd-t7-5.md +++ b/content/2.defense-systems/pd-t7-5.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Vassallo, C. N., Doering, C. R., Littlehale, M. L., Teodoro, G. I. C. & Laub, M. T. A functional selection reveals previously undetected anti-phage defence systems in the E. coli pangenome. Nat Microbiol 7, 1568-1579 (2022).\*\* -The ancient, ongoing coevolutionary battle between bacteria and their viruses, bacteriophages, has given rise to sophisticated immune systems including restriction-modification and CRISPR-Cas. Many additional anti-phage systems have been identified using computational approaches based on genomic co-location within defence islands, but these screens may not be exhaustive. Here we developed an experimental selection scheme agnostic to genomic context to identify defence systems in 71 diverse E. coli strains. Our results unveil 21 conserved defence systems, none of which were previously detected as enriched in defence islands. Additionally, our work indicates that intact prophages and mobile genetic elements are primary reservoirs and distributors of defence systems in E. coli, with defence systems typically carried in specific locations or hotspots. These hotspots encode dozens of additional uncharacterized defence system candidates. Our findings reveal an extended landscape of antiviral immunity in E. coli and provide an approach for mapping defence systems in other species. +::article-doi-list +--- +items: + - 10.1038/s41564-022-01219-4 +--- +:: diff --git a/content/2.defense-systems/pfiat.md b/content/2.defense-systems/pfiat.md index e0effbc2340ba7bf5fbfef72159f8084eee4a9c5..5f8155e980c15be964f8b502d82797f76841cf66 100644 --- a/content/2.defense-systems/pfiat.md +++ b/content/2.defense-systems/pfiat.md @@ -24,6 +24,10 @@ Among the 22k complete genomes of RefSeq, this system is present in 819 genomes ## Relevant abstracts -\*\*Li, Y. et al. Prophage encoding toxin/antitoxin system PfiT/PfiA inhibits Pf4 production in Pseudomonas aeruginosa. Microb Biotechnol 13, 1132-1144 (2020).\*\* -Pf prophages are ssDNA filamentous prophages that are prevalent among various Pseudomonas aeruginosa strains. The genomes of Pf prophages contain not only core genes encoding functions involved in phage replication, structure and assembly but also accessory genes. By studying the accessory genes in the Pf4 prophage in P. aeruginosa PAO1, we provided experimental evidence to demonstrate that PA0729 and the upstream ORF Rorf0727 near the right attachment site of Pf4 form a type II toxin/antitoxin (TA) pair. Importantly, we found that the deletion of the toxin gene PA0729 greatly increased Pf4 phage production. We thus suggest the toxin PA0729 be named PfiT for Pf4 inhibition toxin and Rorf0727 be named PfiA for PfiT antitoxin. The PfiT toxin directly binds to PfiA and functions as a corepressor of PfiA for the TA operon. The PfiAT complex exhibited autoregulation by binding to a palindrome (5'-AATTCN5 GTTAA-3') overlapping the -35 region of the TA operon. The deletion of pfiT disrupted TA autoregulation and activated pfiA expression. Additionally, the deletion of pfiT also activated the expression of the replication initiation factor gene PA0727. Moreover, the Pf4 phage released from the pfiT deletion mutant overcame the immunity provided by the phage repressor Pf4r. Therefore, this study reveals that the TA systems in Pf prophages can regulate phage production and phage immunity, providing new insights into the function of TAs in mobile genetic elements. +::article-doi-list +--- +items: + - 10.1111/1751-7915.13570 +--- +:: diff --git a/content/2.defense-systems/pif.md b/content/2.defense-systems/pif.md index 245bfc89d0dbe4fa3bb37c1716562cc3c1d203e0..ebbec7c797ce628f21c8d1f8504bd9cd14fa0ec4 100644 --- a/content/2.defense-systems/pif.md +++ b/content/2.defense-systems/pif.md @@ -30,12 +30,12 @@ A system from \*Escherichia coli F-plasmid\* in \*Escherichia coli\* has an anti ## Relevant abstracts -\*\*Cheng, X., Wang, W. & Molineux, I. J. F exclusion of bacteriophage T7 occurs at the cell membrane. Virology 326, 340-352 (2004).\*\* -The F plasmid PifA protein, known to be the cause of F exclusion of bacteriophage T7, is shown to be a membrane-associated protein. No transmembrane domains of PifA were located. In contrast, T7 gp1.2 and gp10, the two phage proteins that trigger phage exclusion, are both soluble cytoplasmic proteins. The Escherichia coli FxsA protein, which, at higher concentrations than found in wild-type cells, protects T7 from exclusion, is shown to interact with PifA. FxsA is a polytopic membrane protein with four transmembrane segments and a long cytoplasmic C-terminal tail. This tail is not important in alleviating F exclusion and can be deleted; in contrast, the fourth transmembrane segment of FxsA is critical in allowing wild-type T7 to grow in the presence of F PifA. These data suggest that the primary event that triggers the exclusion process occurs at the cytoplasmic membrane and that FxsA sequesters PifA so that membrane damage is minimized. - -\*\*Cram, D., Ray, A. & Skurray, R. Molecular analysis of F plasmid pif region specifying abortive infection of T7 phage. Mol Gen Genet 197, 137-142 (1984).\*\* -We report the molecular cloning of the pif region of the F plasmid and its physical dissection by subcloning and deletion analysis. Examination of the polypeptide products synthesized in maxicells by plasmids carrying defined pif sequences has shown that the region specifies at least two proteins of molecular weights 80,000 and 40,000, the genes for which appear to lie in the same transcriptional unit. In addition, analysis of pif-lacZ fusion plasmids has detected a pif promoter and determined the direction of transcription across the pif region. - -\*\*Schmitt, C. K., Kemp, P. & Molineux, I. J. Genes 1.2 and 10 of bacteriophages T3 and T7 determine the permeability lesions observed in infected cells of Escherichia coli expressing the F plasmid gene pifA. J Bacteriol 173, 6507-6514 (1991).\*\* -Infections of F plasmid-containing strains of Escherichia coli by bacteriophage T7 result in membrane damage that allows nucleotides to exude from the infected cell into the culture medium. Only pifA of the F pif operon is necessary for "leakiness" of the T7-infected cell. Expression of either T7 gene 1.2 or gene 10 is sufficient to cause leakiness, since infections by phage containing null mutations in both of these genes do not result in permeability changes of the F-containing cell. Even in the absence of phage infection, expression from plasmids of either gene 1.2 or 10 can cause permeability changes, particularly of F plasmid-containing cells. In contrast, gene 1.2 of the related bacteriophage T3 prevents leakiness of the infected cell. In the absence of T3 gene 1.2 function, expression of gene 10 causes membrane damage that allows nucleotides to leak from the cell. Genes 1.2 and 10 of both T3 and T7 are the two genes involved in determining resistance or sensitivity to F exclusion; F exclusion and leakiness of the phage-infected cell are therefore closely related phenomena. However, since leakiness of the infected cell does not necessarily result in phage exclusion, it cannot be used as a predictor of an abortive infection. +::article-doi-list +--- +items: + - 10.1007/BF00327934 + - 10.1016/j.virol.2004.06.001 + - 10.1128/jb.173.20.6507-6514.1991 +--- +:: diff --git a/content/2.defense-systems/prrc.md b/content/2.defense-systems/prrc.md index 6f57554b930fadafe030d59807a2913c0c21bd7c..1ce9dea5e5b2d8185a50f78d8403005ea97d39ac 100644 --- a/content/2.defense-systems/prrc.md +++ b/content/2.defense-systems/prrc.md @@ -30,9 +30,11 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Penner, M., Morad, I., Snyder, L. & Kaufmann, G. Phage T4-coded Stp: double-edged effector of coupled DNA and tRNA-restriction systems. J Mol Biol 249, 857-868 (1995).\*\* -The optional Escherichia coli prr locus encodes two physically associated restriction systems: the type IC DNA restriction-modification enzyme EcoprrI and the tRNA(Lys)-specific anticodon nuclease, specified by the PrrC polypeptide. Anticodon nuclease is kept latent as a result of this interaction. The activation of anticodon nuclease, upon infection by phage T4, may cause depletion of tRNA(Lys) and, consequently, abolition of T4 protein synthesis. However, this effect is counteracted by the repair of tRNA(Lys) in consecutive reactions catalysed by the phage enzymes polynucleotide kinase and RNA ligase. Stp, a short polypeptide encoded by phage T4, has been implicated with activation of the anticodon nuclease. Here we confirm this notion and also demonstrate a second function of Stp: inhibition of EcoprrI restriction. Both effects depend, in general, on the same residues within the N-proximal 18 residue region of Stp. We propose that Stp alters the conformation of EcoprrI and, consequently, of PrrC, allowing activation of the latent anticodon nuclease. Presumably, Stp evolved to offset a DNA restriction system of the host cell but was turned, eventually, against the phage as an activator of the appended tRNA restriction enzyme. - -\*\*Uzan, M. & Miller, E. S. Post-transcriptional control by bacteriophage T4: mRNA decay and inhibition of translation initiation. Virology Journal 7, 360 (2010).\*\* -Over 50 years of biological research with bacteriophage T4 includes notable discoveries in post-transcriptional control, including the genetic code, mRNA, and tRNA; the very foundations of molecular biology. In this review we compile the past 10 - 15 year literature on RNA-protein interactions with T4 and some of its related phages, with particular focus on advances in mRNA decay and processing, and on translational repression. Binding of T4 proteins RegB, RegA, gp32 and gp43 to their cognate target RNAs has been characterized. For several of these, further study is needed for an atomic-level perspective, where resolved structures of RNA-protein complexes are awaiting investigation. Other features of post-transcriptional control are also summarized. These include: RNA structure at translation initiation regions that either inhibit or promote translation initiation; programmed translational bypassing, where T4 orchestrates ribosome bypass of a 50 nucleotide mRNA sequence; phage exclusion systems that involve T4-mediated activation of a latent endoribonuclease (PrrC) and cofactor-assisted activation of EF-Tu proteolysis (Gol-Lit); and potentially important findings on ADP-ribosylation (by Alt and Mod enzymes) of ribosome-associated proteins that might broadly impact protein synthesis in the infected cell. Many of these problems can continue to be addressed with T4, whereas the growing database of T4-related phage genome sequences provides new resources and potentially new phage-host systems to extend the work into a broader biological, evolutionary context. +::article-doi-list +--- +items: + - 10.1006/jmbi.1995.0343 + - 10.1186/1743-422X-7-360 +--- +:: diff --git a/content/2.defense-systems/psyrta.md b/content/2.defense-systems/psyrta.md index 152dad509be61e96ac40b9ca38043940855bae63..3bc102d2a3dd89d0bf8466001f25709357f4ccbd 100644 --- a/content/2.defense-systems/psyrta.md +++ b/content/2.defense-systems/psyrta.md @@ -30,9 +30,11 @@ A system from \*Bacillus sp. FJAT-29814\* in \*Escherichia coli\* has an anti-ph ## Relevant abstracts -\*\*Millman, A. et al. An expanded arsenal of immune systems that protect bacteria from phages. Cell Host Microbe 30, 1556-1569.e5 (2022).\*\* -Bacterial anti-phage systems are frequently clustered in microbial genomes, forming defense islands. This property enabled the recent discovery of multiple defense systems based on their genomic co-localization with known systems, but the full arsenal of anti-phage mechanisms remains unknown. We report the discovery of 21 defense systems that protect bacteria from phages, based on computational genomic analyses and phage-infection experiments. We identified multiple systems with domains involved in eukaryotic antiviral immunity, including those homologous to the ubiquitin-like ISG15 protein, dynamin-like domains, and SEFIR domains, and show their participation in bacterial defenses. Additional systems include domains predicted to manipulate DNA and RNA molecules, alongside toxin-antitoxin systems shown here to function in anti-phage defense. These systems are widely distributed in microbial genomes, and in some bacteria, they form a considerable fraction of the immune arsenal. Our data substantially expand the inventory of defense systems utilized by bacteria to counteract phage infection. - -\*\*Sberro, H. et al. Discovery of functional toxin/antitoxin systems in bacteria by shotgun cloning. Mol Cell 50, 136-148 (2013).\*\* -Toxin-antitoxin (TA) modules, composed of a toxic protein and a counteracting antitoxin, play important roles in bacterial physiology. We examined the experimental insertion of 1.5 million genes from 388 microbial genomes into an Escherichia coli host using more than 8.5 million random clones. This revealed hundreds of genes (toxins) that could only be cloned when the neighboring gene (antitoxin) was present on the same clone. Clustering of these genes revealed TA families widespread in bacterial genomes, some of which deviate from the classical characteristics previously described for such modules. Introduction of these genes into E. coli validated that the toxin toxicity is mitigated by the antitoxin. Infection experiments with T7 phage showed that two of the new modules can provide resistance against phage. Moreover, our experiments revealed an "antidefense" protein in phage T7 that neutralizes phage resistance. Our results expose active fronts in the arms race between bacteria and phage. +::article-doi-list +--- +items: + - 10.1016/j.chom.2022.09.017 + - 10.1016/j.molcel.2013.02.002 +--- +:: diff --git a/content/2.defense-systems/pycsar.md b/content/2.defense-systems/pycsar.md index 484c30983457c14a33fc8cda738e91d88cb79170..196eb31d777da6d1f4474fef908260d543e586e4 100644 --- a/content/2.defense-systems/pycsar.md +++ b/content/2.defense-systems/pycsar.md @@ -32,6 +32,10 @@ A system from \*Xanthomonas perforans\* in \*Escherichia coli\* has an anti-phag ## Relevant abstracts -\*\*Tal, N. et al. Cyclic CMP and cyclic UMP mediate bacterial immunity against phages. Cell 184, 5728-5739.e16 (2021).\*\* -The cyclic pyrimidines 3',5'-cyclic cytidine monophosphate (cCMP) and 3',5'-cyclic uridine monophosphate (cUMP) have been reported in multiple organisms and cell types. As opposed to the cyclic nucleotides 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP), which are second messenger molecules with well-established regulatory roles across all domains of life, the biological role of cyclic pyrimidines has remained unclear. Here we report that cCMP and cUMP are second messengers functioning in bacterial immunity against viruses. We discovered a family of bacterial pyrimidine cyclase enzymes that specifically synthesize cCMP and cUMP following phage infection and demonstrate that these molecules activate immune effectors that execute an antiviral response. A crystal structure of a uridylate cyclase enzyme from this family explains the molecular mechanism of selectivity for pyrimidines as cyclization substrates. Defense systems encoding pyrimidine cyclases, denoted here Pycsar (pyrimidine cyclase system for antiphage resistance), are widespread in prokaryotes. Our results assign clear biological function to cCMP and cUMP as immunity signaling molecules in bacteria. +::article-doi-list +--- +items: + - 10.1016/j.cell.2021.09.031 +--- +:: diff --git a/content/2.defense-systems/retron.md b/content/2.defense-systems/retron.md index c9cd89b27b812dd1bd4c1767b8a5a740464cdd21..65a83b955ffba3f9b427fd96bf1c19d4bd89bb25 100644 --- a/content/2.defense-systems/retron.md +++ b/content/2.defense-systems/retron.md @@ -132,9 +132,11 @@ Subsystem Retron-Eco1 with a system from \*Escherichia coli\* in \*Escherichia c ## Relevant abstracts -\*\*Mestre, M. R., González-Delgado, A., Gutiérrez-Rus, L. I., MartÃnez-Abarca, F. & Toro, N. Systematic prediction of genes functionally associated with bacterial retrons and classification of the encoded tripartite systems. Nucleic Acids Research 48, 12632-12647 (2020).\*\* -Bacterial retrons consist of a reverse transcriptase (RT) and a contiguous non-coding RNA (ncRNA) gene. One third of annotated retrons carry additional open reading frames (ORFs), the contribution and significance of which in retron biology remains to be determined. In this study we developed a computational pipeline for the systematic prediction of genes specifically associated with retron RTs based on a previously reported large dataset representative of the diversity of prokaryotic RTs. We found that retrons generally comprise a tripartite system composed of the ncRNA, the RT and an additional protein or RT-fused domain with diverse enzymatic functions. These retron systems are highly modular, and their components have coevolved to different extents. Based on the additional module, we classified retrons into 13 types, some of which include additional variants. Our findings provide a basis for future studies on the biological function of retrons and for expanding their biotechnological applications. - -\*\*Millman, A. et al. Bacterial Retrons Function In Anti-Phage Defense. Cell 183, 1551-1561.e12 (2020).\*\* -Retrons are bacterial genetic elements comprised of a reverse transcriptase (RT) and a non-coding RNA (ncRNA). The RT uses the ncRNA as template, generating a chimeric RNA/DNA molecule in which the RNA and DNA components are covalently linked. Although retrons were discovered three decades ago, their function remained unknown. We report that retrons function as anti-phage defense systems. The defensive unit is composed of three components: the RT, the ncRNA, and an effector protein. We examined multiple retron systems and show that they confer defense against a broad range of phages via abortive infection. Focusing on retron Ec48, we show evidence that it "guards" RecBCD, a complex with central anti-phage functions in bacteria. Inhibition of RecBCD by phage proteins activates the retron, leading to abortive infection and cell death. Thus, the Ec48 retron forms a second line of defense that is triggered if the first lines of defense have collapsed. +::article-doi-list +--- +items: + - 10.1016/j.cell.2020.09.065 + - 10.1093/nar/gkaa1149 +--- +:: diff --git a/content/2.defense-systems/rexab.md b/content/2.defense-systems/rexab.md index f46c6900c0c28d117ae28d4503dbd254af9d8d15..90b98180dfe6381f1b7a1ffe48557549fb9de5a7 100644 --- a/content/2.defense-systems/rexab.md +++ b/content/2.defense-systems/rexab.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli lambda prophage\* in \*Escherichia coli\* has a ## Relevant abstracts -\*\*Parma, D. H. et al. The Rex system of bacteriophage lambda: tolerance and altruistic cell death. Genes Dev 6, 497-510 (1992).\*\* -The rexA and rexB genes of bacteriophage lambda encode a two-component system that aborts lytic growth of bacterial viruses. Rex exclusion is characterized by termination of macromolecular synthesis, loss of active transport, the hydrolysis of ATP, and cell death. By analogy to colicins E1 and K, these results can be explained by depolarization of the cytoplasmic membrane. We have fractionated cells to determine the intracellular location of the RexB protein and made RexB-alkaline phosphatase fusions to analyze its membrane topology. The RexB protein appears to be a polytopic transmembrane protein. We suggest that RexB proteins form ion channels that, in response to lytic growth of bacteriophages, depolarize the cytoplasmic membrane. The Rex system requires a mechanism to prevent lambda itself from being excluded during lytic growth. We have determined that overexpression of RexB in lambda lysogens prevents the exclusion of both T4 rII mutants and lambda ren mutants. We suspect that overexpression of RexB is the basis for preventing self-exclusion following the induction of a lambda lysogen and that RexB overexpression is accomplished through transcriptional regulation. +::article-doi-list +--- +items: + - 10.1101/gad.6.3.497 +--- +:: diff --git a/content/2.defense-systems/rloc.md b/content/2.defense-systems/rloc.md index c23cf8e5be921b9652462226a33d18ea549c74db..68367c6d398c12c976ca44a1f25c03f64497add0 100644 --- a/content/2.defense-systems/rloc.md +++ b/content/2.defense-systems/rloc.md @@ -30,9 +30,11 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Bitton, L., Klaiman, D. & Kaufmann, G. Phage T4-induced DNA breaks activate a tRNA repair-defying anticodon nuclease. Mol Microbiol 97, 898-910 (2015).\*\* -The natural role of the conserved bacterial anticodon nuclease (ACNase) RloC is not known, but traits that set it apart from the homologous phage T4-excluding ACNase PrrC could provide relevant clues. PrrC is silenced by a genetically linked DNA restriction-modification (RM) protein and turned on by a phage-encoded DNA restriction inhibitor. In contrast, RloC is rarely linked to an RM protein, and its ACNase is regulated by an internal switch responsive to double-stranded DNA breaks. Moreover, PrrC nicks the tRNA substrate, whereas RloC excises the wobble nucleotide. These distinctions suggested that (i) T4 and related phage that degrade their host DNA will activate RloC and (ii) the tRNA species consequently disrupted will not be restored by phage tRNA repair enzymes that counteract PrrC. Consistent with these predictions we show that Acinetobacter baylyi?RloC expressed in Escherichia coli is activated by wild-type phage T4 but not by a mutant impaired in host DNA degradation. Moreover, host and T4 tRNA species disrupted by the activated ACNase were not restored by T4's tRNA repair system. Nonetheless, T4's plating efficiency was inefficiently impaired by AbaRloC, presumably due to a decoy function of the phage encoded tRNA target, the absence of which exacerbated the restriction. - -\*\*Davidov, E. & Kaufmann, G. RloC: a wobble nucleotide-excising and zinc-responsive bacterial tRNase. Mol Microbiol 69, 1560-1574 (2008).\*\* -The conserved bacterial protein RloC, a distant homologue of the tRNA(Lys) anticodon nuclease (ACNase) PrrC, is shown here to act as a wobble nucleotide-excising and Zn(++)-responsive tRNase. The more familiar PrrC is silenced by a genetically linked type I DNA restriction-modification (R-M) enzyme, activated by a phage anti-DNA restriction factor and counteracted by phage tRNA repair enzymes. RloC shares PrrC's ABC ATPase motifs and catalytic ACNase triad but features a distinct zinc-hook/coiled-coil insert that renders its ATPase domain similar to Rad50 and related DNA repair proteins. Geobacillus kaustophilus RloC expressed in Escherichia coli exhibited ACNase activity that differed from PrrC's in substrate preference and ability to excise the wobble nucleotide. The latter specificity could impede reversal by phage tRNA repair enzymes and account perhaps for RloC's more frequent occurrence. Mutagenesis and functional assays confirmed RloC's catalytic triad assignment and implicated its zinc hook in regulating the ACNase function. Unlike PrrC, RloC is rarely linked to a type I R-M system but other genomic attributes suggest their possible interaction in trans. As DNA damage alleviates type I DNA restriction, we further propose that these related perturbations prompt RloC to disable translation and thus ward off phage escaping DNA restriction during the recovery from DNA damage. +::article-doi-list +--- +items: + - 10.1111/j.1365-2958.2008.06387.x + - 10.1111/mmi.13074 +--- +:: diff --git a/content/2.defense-systems/rm.md b/content/2.defense-systems/rm.md index 7a4392c52da19e6adfc23f4d3dbd54ef23db4112..58ec8aabbd186ef29651c1ed8de3783a617e8d32 100644 --- a/content/2.defense-systems/rm.md +++ b/content/2.defense-systems/rm.md @@ -40,6 +40,10 @@ Among the 22k complete genomes of RefSeq, this system is present in 19087 genome ## Relevant abstracts -\*\*Oliveira, P. H., Touchon, M. & Rocha, E. P. C. The interplay of restriction-modification systems with mobile genetic elements and their prokaryotic hosts. Nucleic Acids Res 42, 10618-10631 (2014).\*\* -The roles of restriction-modification (R-M) systems in providing immunity against horizontal gene transfer (HGT) and in stabilizing mobile genetic elements (MGEs) have been much debated. However, few studies have precisely addressed the distribution of these systems in light of HGT, its mechanisms and its vectors. We analyzed the distribution of R-M systems in 2261 prokaryote genomes and found their frequency to be strongly dependent on the presence of MGEs, CRISPR-Cas systems, integrons and natural transformation. Yet R-M systems are rare in plasmids, in prophages and nearly absent from other phages. Their abundance depends on genome size for small genomes where it relates with HGT but saturates at two occurrences per genome. Chromosomal R-M systems might evolve under cycles of purifying and relaxed selection, where sequence conservation depends on the biochemical activity and complexity of the system and total gene loss is frequent. Surprisingly, analysis of 43 pan-genomes suggests that solitary R-M genes rarely arise from the degradation of R-M systems. Solitary genes are transferred by large MGEs, whereas complete systems are more frequently transferred autonomously or in small MGEs. Our results suggest means of testing the roles for R-M systems and their associations with MGEs. +::article-doi-list +--- +items: + - 10.1093/nar/gku734 +--- +:: diff --git a/content/2.defense-systems/rnlab.md b/content/2.defense-systems/rnlab.md index a79f672cfc52a0c167cc51f2e0ffe484206c68a9..bd38e210973a74ab8d8998c5c756f14b90e1f2fa 100644 --- a/content/2.defense-systems/rnlab.md +++ b/content/2.defense-systems/rnlab.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Koga, M., Otsuka, Y., Lemire, S. & Yonesaki, T. Escherichia coli rnlA and rnlB Compose a Novel Toxin-Antitoxin System. Genetics 187, 123-130 (2011).\*\* -RNase LS was originally identified as a potential antagonist of bacteriophage T4 infection. When T4 dmd is defective, RNase LS activity rapidly increases after T4 infection and cleaves T4 mRNAs to antagonize T4 reproduction. Here we show that rnlA, a structural gene of RNase LS, encodes a novel toxin, and that rnlB (formally yfjO), located immediately downstream of rnlA, encodes an antitoxin against RnlA. Ectopic expression of RnlA caused inhibition of cell growth and rapid degradation of mRNAs in ?rnlAB cells. On the other hand, RnlB neutralized these RnlA effects. Furthermore, overexpression of RnlB in wild-type cells could completely suppress the growth defect of a T4 dmd mutant, that is, excess RnlB inhibited RNase LS activity. Pull-down analysis showed a specific interaction between RnlA and RnlB. Compared to RnlA, RnlB was extremely unstable, being degraded by ClpXP and Lon proteases, and this instability may increase RNase LS activity after T4 infection. All of these results suggested that rnlA-rnlB define a new toxin-antitoxin (TA) system. +::article-doi-list +--- +items: + - 10.1534/genetics.110.121798 +--- +:: diff --git a/content/2.defense-systems/rosmerta.md b/content/2.defense-systems/rosmerta.md index d9d81ccd5e153e24276da85681e110ed425dfb57..d68025dae987db70a690eff2c2c22d634fb05099 100644 --- a/content/2.defense-systems/rosmerta.md +++ b/content/2.defense-systems/rosmerta.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Millman, A. et al. An expanded arsenal of immune systems that protect bacteria from phages. Cell Host Microbe 30, 1556-1569.e5 (2022).\*\* -Bacterial anti-phage systems are frequently clustered in microbial genomes, forming defense islands. This property enabled the recent discovery of multiple defense systems based on their genomic co-localization with known systems, but the full arsenal of anti-phage mechanisms remains unknown. We report the discovery of 21 defense systems that protect bacteria from phages, based on computational genomic analyses and phage-infection experiments. We identified multiple systems with domains involved in eukaryotic antiviral immunity, including those homologous to the ubiquitin-like ISG15 protein, dynamin-like domains, and SEFIR domains, and show their participation in bacterial defenses. Additional systems include domains predicted to manipulate DNA and RNA molecules, alongside toxin-antitoxin systems shown here to function in anti-phage defense. These systems are widely distributed in microbial genomes, and in some bacteria, they form a considerable fraction of the immune arsenal. Our data substantially expand the inventory of defense systems utilized by bacteria to counteract phage infection. +::article-doi-list +--- +items: + - 10.1016/j.chom.2022.09.017 +--- +:: diff --git a/content/2.defense-systems/rst_2tm_1tm_tir.md b/content/2.defense-systems/rst_2tm_1tm_tir.md index 64af1fa292500675752b4f8a04986547a2e372dc..0d27a2c4f446ec6f18067f2f006ee64718aac7a8 100644 --- a/content/2.defense-systems/rst_2tm_1tm_tir.md +++ b/content/2.defense-systems/rst_2tm_1tm_tir.md @@ -24,6 +24,10 @@ Among the 22k complete genomes of RefSeq, this system is present in 2 genomes (0 ## Relevant abstracts -\*\*Rousset, F. et al. Phages and their satellites encode hotspots of antiviral systems. Cell Host & Microbe 30, 740-753.e5 (2022).\*\* -Bacteria carry diverse genetic systems to defend against viral infection, some of which are found within prophages where they inhibit competing viruses. Phage satellites pose additional pressures on phages by hijacking key viral elements to their own benefit. Here, we show that E. coli P2-like phages and their parasitic P4-like satellites carry hotspots of genetic variation containing reservoirs of anti-phage systems. We validate the activity of diverse systems and describe PARIS, an abortive infection system triggered by a phage-encoded anti-restriction protein. Antiviral hotspots participate in inter-viral competition and shape dynamics between the bacterial host, P2-like phages, and P4-like satellites. Notably, the anti-phage activity of satellites can benefit the helper phage during competition with virulent phages, turning a parasitic relationship into a mutualistic one. Anti-phage hotspots are present across distant species and constitute a substantial source of systems that participate in the competition between mobile genetic elements. +::article-doi-list +--- +items: + - 10.1016/j.chom.2022.02.018 +--- +:: diff --git a/content/2.defense-systems/rst_3hp.md b/content/2.defense-systems/rst_3hp.md index f255acc992582804c157ab449653432ba9fbfa8e..b74e99366da20011485d63f46952db0d82014a3c 100644 --- a/content/2.defense-systems/rst_3hp.md +++ b/content/2.defense-systems/rst_3hp.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli (P2 loci)\* in \*Escherichia coli\* has an anti ## Relevant abstracts -\*\*Rousset, F. et al. Phages and their satellites encode hotspots of antiviral systems. Cell Host & Microbe 30, 740-753.e5 (2022).\*\* -Bacteria carry diverse genetic systems to defend against viral infection, some of which are found within prophages where they inhibit competing viruses. Phage satellites pose additional pressures on phages by hijacking key viral elements to their own benefit. Here, we show that E. coli P2-like phages and their parasitic P4-like satellites carry hotspots of genetic variation containing reservoirs of anti-phage systems. We validate the activity of diverse systems and describe PARIS, an abortive infection system triggered by a phage-encoded anti-restriction protein. Antiviral hotspots participate in inter-viral competition and shape dynamics between the bacterial host, P2-like phages, and P4-like satellites. Notably, the anti-phage activity of satellites can benefit the helper phage during competition with virulent phages, turning a parasitic relationship into a mutualistic one. Anti-phage hotspots are present across distant species and constitute a substantial source of systems that participate in the competition between mobile genetic elements. +::article-doi-list +--- +items: + - 10.1016/j.chom.2022.02.018 +--- +:: diff --git a/content/2.defense-systems/rst_duf4238.md b/content/2.defense-systems/rst_duf4238.md index f86d4631e631f87dfc65937f10148dce8ea7347f..7ca091d690661caf5a4cd91950609b4efbb74341 100644 --- a/content/2.defense-systems/rst_duf4238.md +++ b/content/2.defense-systems/rst_duf4238.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli (P2 loci)\* in \*Escherichia coli\* has an anti ## Relevant abstracts -\*\*Rousset, F. et al. Phages and their satellites encode hotspots of antiviral systems. Cell Host & Microbe 30, 740-753.e5 (2022).\*\* -Bacteria carry diverse genetic systems to defend against viral infection, some of which are found within prophages where they inhibit competing viruses. Phage satellites pose additional pressures on phages by hijacking key viral elements to their own benefit. Here, we show that E. coli P2-like phages and their parasitic P4-like satellites carry hotspots of genetic variation containing reservoirs of anti-phage systems. We validate the activity of diverse systems and describe PARIS, an abortive infection system triggered by a phage-encoded anti-restriction protein. Antiviral hotspots participate in inter-viral competition and shape dynamics between the bacterial host, P2-like phages, and P4-like satellites. Notably, the anti-phage activity of satellites can benefit the helper phage during competition with virulent phages, turning a parasitic relationship into a mutualistic one. Anti-phage hotspots are present across distant species and constitute a substantial source of systems that participate in the competition between mobile genetic elements. +::article-doi-list +--- +items: + - 10.1016/j.chom.2022.02.018 +--- +:: diff --git a/content/2.defense-systems/rst_gop_beta_cll.md b/content/2.defense-systems/rst_gop_beta_cll.md index 6c421e947df3e69fcb40cad39841af85f4973ea6..20e9852e66fef6b630d16900430d1bc56ba26823 100644 --- a/content/2.defense-systems/rst_gop_beta_cll.md +++ b/content/2.defense-systems/rst_gop_beta_cll.md @@ -30,6 +30,10 @@ A system from \*Enterobacteria phage P4\* in \*Escherichia coli\* has an anti-ph ## Relevant abstracts -\*\*Rousset, F. et al. Phages and their satellites encode hotspots of antiviral systems. Cell Host & Microbe 30, 740-753.e5 (2022).\*\* -Bacteria carry diverse genetic systems to defend against viral infection, some of which are found within prophages where they inhibit competing viruses. Phage satellites pose additional pressures on phages by hijacking key viral elements to their own benefit. Here, we show that E. coli P2-like phages and their parasitic P4-like satellites carry hotspots of genetic variation containing reservoirs of anti-phage systems. We validate the activity of diverse systems and describe PARIS, an abortive infection system triggered by a phage-encoded anti-restriction protein. Antiviral hotspots participate in inter-viral competition and shape dynamics between the bacterial host, P2-like phages, and P4-like satellites. Notably, the anti-phage activity of satellites can benefit the helper phage during competition with virulent phages, turning a parasitic relationship into a mutualistic one. Anti-phage hotspots are present across distant species and constitute a substantial source of systems that participate in the competition between mobile genetic elements. +::article-doi-list +--- +items: + - 10.1016/j.chom.2022.02.018 +--- +:: diff --git a/content/2.defense-systems/rst_helicaseduf2290.md b/content/2.defense-systems/rst_helicaseduf2290.md index 0a8b802006e7e88d2c00a4d7cf8d6d43cc6d8209..55374a765b580a440925d339d4ad92416348e92f 100644 --- a/content/2.defense-systems/rst_helicaseduf2290.md +++ b/content/2.defense-systems/rst_helicaseduf2290.md @@ -30,6 +30,10 @@ A system from \*Klebsiella pneumoniae (P4 loci)\* in \*Escherichia coli\* has an ## Relevant abstracts -\*\*Rousset, F. et al. Phages and their satellites encode hotspots of antiviral systems. Cell Host & Microbe 30, 740-753.e5 (2022).\*\* -Bacteria carry diverse genetic systems to defend against viral infection, some of which are found within prophages where they inhibit competing viruses. Phage satellites pose additional pressures on phages by hijacking key viral elements to their own benefit. Here, we show that E. coli P2-like phages and their parasitic P4-like satellites carry hotspots of genetic variation containing reservoirs of anti-phage systems. We validate the activity of diverse systems and describe PARIS, an abortive infection system triggered by a phage-encoded anti-restriction protein. Antiviral hotspots participate in inter-viral competition and shape dynamics between the bacterial host, P2-like phages, and P4-like satellites. Notably, the anti-phage activity of satellites can benefit the helper phage during competition with virulent phages, turning a parasitic relationship into a mutualistic one. Anti-phage hotspots are present across distant species and constitute a substantial source of systems that participate in the competition between mobile genetic elements. +::article-doi-list +--- +items: + - 10.1016/j.chom.2022.02.018 +--- +:: diff --git a/content/2.defense-systems/rst_hydrolase-3tm.md b/content/2.defense-systems/rst_hydrolase-3tm.md index 002c33ef11469ef554e46d83d6472a52f062f4d7..a03da92263d3c43745407e90cbbc530fa125a046 100644 --- a/content/2.defense-systems/rst_hydrolase-3tm.md +++ b/content/2.defense-systems/rst_hydrolase-3tm.md @@ -30,3 +30,10 @@ A system from \*Escherichia coli (P4 loci)\* in \*Escherichia coli\* has an anti ## Relevant abstracts +::article-doi-list +--- +items: + - 10.1016/j.chom.2022.02.018 + +--- +:: diff --git a/content/2.defense-systems/rst_paris.md b/content/2.defense-systems/rst_paris.md index 283184b583687a36af6afd52d26ec06a62c2b88d..52efa098f590df5d4758e438764fb4cdee85fdae 100644 --- a/content/2.defense-systems/rst_paris.md +++ b/content/2.defense-systems/rst_paris.md @@ -50,6 +50,10 @@ Subsystem Paris 2 with a system from \*Escherichia coli (P4 loci)\* in \*Escheri ## Relevant abstracts -\*\*Rousset, F. et al. Phages and their satellites encode hotspots of antiviral systems. Cell Host & Microbe 30, 740-753.e5 (2022).\*\* -Bacteria carry diverse genetic systems to defend against viral infection, some of which are found within prophages where they inhibit competing viruses. Phage satellites pose additional pressures on phages by hijacking key viral elements to their own benefit. Here, we show that E. coli P2-like phages and their parasitic P4-like satellites carry hotspots of genetic variation containing reservoirs of anti-phage systems. We validate the activity of diverse systems and describe PARIS, an abortive infection system triggered by a phage-encoded anti-restriction protein. Antiviral hotspots participate in inter-viral competition and shape dynamics between the bacterial host, P2-like phages, and P4-like satellites. Notably, the anti-phage activity of satellites can benefit the helper phage during competition with virulent phages, turning a parasitic relationship into a mutualistic one. Anti-phage hotspots are present across distant species and constitute a substantial source of systems that participate in the competition between mobile genetic elements. +::article-doi-list +--- +items: + - 10.1016/j.chom.2022.02.018 +--- +:: diff --git a/content/2.defense-systems/rst_rt-nitrilase-tm.md b/content/2.defense-systems/rst_rt-nitrilase-tm.md index 21fe821dcec34d72decb6f62491cdeb8bf5faa0e..cd3a5a9f4d8afaf6b6581081ff9f18e48e778c79 100644 --- a/content/2.defense-systems/rst_rt-nitrilase-tm.md +++ b/content/2.defense-systems/rst_rt-nitrilase-tm.md @@ -30,3 +30,10 @@ A system from \*Escherichia coli (P4 loci)\* in \*Escherichia coli\* has an anti ## Relevant abstracts +::article-doi-list +--- +items: + - 10.1016/j.chom.2022.02.018 + +--- +:: diff --git a/content/2.defense-systems/rst_tir-nlr.md b/content/2.defense-systems/rst_tir-nlr.md index 76bfa9d18e11d0d37b5f8cf2b4323bc0cfeec864..74ebbafc08b15a35177a6d2f7a136fde0a266fde 100644 --- a/content/2.defense-systems/rst_tir-nlr.md +++ b/content/2.defense-systems/rst_tir-nlr.md @@ -30,6 +30,10 @@ A system from \*Klebsiella pneumoniae (P4 loci)\* in \*Escherichia coli\* has an ## Relevant abstracts -\*\*Rousset, F. et al. Phages and their satellites encode hotspots of antiviral systems. Cell Host & Microbe 30, 740-753.e5 (2022).\*\* -Bacteria carry diverse genetic systems to defend against viral infection, some of which are found within prophages where they inhibit competing viruses. Phage satellites pose additional pressures on phages by hijacking key viral elements to their own benefit. Here, we show that E. coli P2-like phages and their parasitic P4-like satellites carry hotspots of genetic variation containing reservoirs of anti-phage systems. We validate the activity of diverse systems and describe PARIS, an abortive infection system triggered by a phage-encoded anti-restriction protein. Antiviral hotspots participate in inter-viral competition and shape dynamics between the bacterial host, P2-like phages, and P4-like satellites. Notably, the anti-phage activity of satellites can benefit the helper phage during competition with virulent phages, turning a parasitic relationship into a mutualistic one. Anti-phage hotspots are present across distant species and constitute a substantial source of systems that participate in the competition between mobile genetic elements. +::article-doi-list +--- +items: + - 10.1016/j.chom.2022.02.018 +--- +:: diff --git a/content/2.defense-systems/sanata.md b/content/2.defense-systems/sanata.md index 475c57bebecdfdacf00c9cefc24daca927660907..2b676b22062b386f01d96e05ead19cff96571a57 100644 --- a/content/2.defense-systems/sanata.md +++ b/content/2.defense-systems/sanata.md @@ -30,6 +30,10 @@ A system from \*Shewanella sp. ANA-3\* in \*Escherichia coli\* has an anti-phage ## Relevant abstracts -\*\*Sberro, H. et al. Discovery of functional toxin/antitoxin systems in bacteria by shotgun cloning. Mol Cell 50, 136-148 (2013).\*\* -Toxin-antitoxin (TA) modules, composed of a toxic protein and a counteracting antitoxin, play important roles in bacterial physiology. We examined the experimental insertion of 1.5 million genes from 388 microbial genomes into an Escherichia coli host using more than 8.5 million random clones. This revealed hundreds of genes (toxins) that could only be cloned when the neighboring gene (antitoxin) was present on the same clone. Clustering of these genes revealed TA families widespread in bacterial genomes, some of which deviate from the classical characteristics previously described for such modules. Introduction of these genes into E. coli validated that the toxin toxicity is mitigated by the antitoxin. Infection experiments with T7 phage showed that two of the new modules can provide resistance against phage. Moreover, our experiments revealed an "antidefense" protein in phage T7 that neutralizes phage resistance. Our results expose active fronts in the arms race between bacteria and phage. +::article-doi-list +--- +items: + - 10.1016/j.molcel.2013.02.002 +--- +:: diff --git a/content/2.defense-systems/septu.md b/content/2.defense-systems/septu.md index 954030e4072f9759abe072fa1bb3bd8cd21a39d3..2bb5aa9ad63c9068fefadbd1af4ce5f2961e676d 100644 --- a/content/2.defense-systems/septu.md +++ b/content/2.defense-systems/septu.md @@ -32,12 +32,12 @@ A system from \*Bacillus weihenstephanensis\* in \*Bacillus subtilis\* has an an ## Relevant abstracts -\*\*Doron, S. et al. Systematic discovery of antiphage defense systems in the microbial pangenome. Science 359, eaar4120 (2018).\*\* -The arms race between bacteria and phages led to the development of sophisticated antiphage defense systems, including CRISPR-Cas and restriction-modification systems. Evidence suggests that known and unknown defense systems are located in "defense islands" in microbial genomes. Here, we comprehensively characterized the bacterial defensive arsenal by examining gene families that are clustered next to known defense genes in prokaryotic genomes. Candidate defense systems were systematically engineered and validated in model bacteria for their antiphage activities. We report nine previously unknown antiphage systems and one antiplasmid system that are widespread in microbes and strongly protect against foreign invaders. These include systems that adopted components of the bacterial flagella and condensin complexes. Our data also suggest a common, ancient ancestry of innate immunity components shared between animals, plants, and bacteria. - -\*\*Millman, A. et al. Bacterial Retrons Function In Anti-Phage Defense. Cell 183, 1551-1561.e12 (2020).\*\* -Retrons are bacterial genetic elements comprised of a reverse transcriptase (RT) and a non-coding RNA (ncRNA). The RT uses the ncRNA as template, generating a chimeric RNA/DNA molecule in which the RNA and DNA components are covalently linked. Although retrons were discovered three decades ago, their function remained unknown. We report that retrons function as anti-phage defense systems. The defensive unit is composed of three components: the RT, the ncRNA, and an effector protein. We examined multiple retron systems and show that they confer defense against a broad range of phages via abortive infection. Focusing on retron Ec48, we show evidence that it "guards" RecBCD, a complex with central anti-phage functions in bacteria. Inhibition of RecBCD by phage proteins activates the retron, leading to abortive infection and cell death. Thus, the Ec48 retron forms a second line of defense that is triggered if the first lines of defense have collapsed. - -\*\*Payne, L. J. et al. Identification and classification of antiviral defence systems in bacteria and archaea with PADLOC reveals new system types. Nucleic Acids Research 49, 10868-10878 (2021).\*\* -To provide protection against viral infection and limit the uptake of mobile genetic elements, bacteria and archaea have evolved many diverse defence systems. The discovery and application of CRISPR-Cas adaptive immune systems has spurred recent interest in the identification and classification of new types of defence systems. Many new defence systems have recently been reported but there is a lack of accessible tools available to identify homologs of these systems in different genomes. Here, we report the Prokaryotic Antiviral Defence LOCator (PADLOC), a flexible and scalable open-source tool for defence system identification. With PADLOC, defence system genes are identified using HMM-based homologue searches, followed by validation of system completeness using gene presence/absence and synteny criteria specified by customisable system classifications. We show that PADLOC identifies defence systems with high accuracy and sensitivity. Our modular approach to organising the HMMs and system classifications allows additional defence systems to be easily integrated into the PADLOC database. To demonstrate application of PADLOC to biological questions, we used PADLOC to identify six new subtypes of known defence systems and a putative novel defence system comprised of a helicase, methylase and ATPase. PADLOC is available as a standalone package (https://github.com/padlocbio/padloc) and as a webserver (https://padloc.otago.ac.nz). +::article-doi-list +--- +items: + - 10.1016/j.cell.2020.09.065 + - 10.1093/nar/gkab883 + - 10.1126/science.aar4120 +--- +:: diff --git a/content/2.defense-systems/shedu.md b/content/2.defense-systems/shedu.md index 6eb32679e9c857d4888c0cb51f4eeaa4778aa47f..144dced8bd09ff4731cd0fb9ba797e802eaccf5c 100644 --- a/content/2.defense-systems/shedu.md +++ b/content/2.defense-systems/shedu.md @@ -30,6 +30,10 @@ A system from \*Bacillus cereus\* in \*Bacillus subtilis\* has an anti-phage eff ## Relevant abstracts -\*\*Doron, S. et al. Systematic discovery of antiphage defense systems in the microbial pangenome. Science 359, eaar4120 (2018).\*\* -The arms race between bacteria and phages led to the development of sophisticated antiphage defense systems, including CRISPR-Cas and restriction-modification systems. Evidence suggests that known and unknown defense systems are located in "defense islands" in microbial genomes. Here, we comprehensively characterized the bacterial defensive arsenal by examining gene families that are clustered next to known defense genes in prokaryotic genomes. Candidate defense systems were systematically engineered and validated in model bacteria for their antiphage activities. We report nine previously unknown antiphage systems and one antiplasmid system that are widespread in microbes and strongly protect against foreign invaders. These include systems that adopted components of the bacterial flagella and condensin complexes. Our data also suggest a common, ancient ancestry of innate immunity components shared between animals, plants, and bacteria. +::article-doi-list +--- +items: + - 10.1126/science.aar4120 +--- +:: diff --git a/content/2.defense-systems/shosta.md b/content/2.defense-systems/shosta.md index a9a4fe5b45f512cde1964c4f41dd2ec8f69c2c9d..8c477503977f59899e7df214b342b1f4ce85c2b7 100644 --- a/content/2.defense-systems/shosta.md +++ b/content/2.defense-systems/shosta.md @@ -32,12 +32,12 @@ A system from \*Escherichia coli (P2 loci)\* in \*Escherichia coli\* has an anti ## Relevant abstracts -\*\*Kimelman, A. et al. A vast collection of microbial genes that are toxic to bacteria. Genome research 22, 802-809 (2012).\*\* -In the process of clone-based genome sequencing, initial assemblies frequently contain cloning gaps that can be resolved using cloning-independent methods, but the reason for their occurrence is largely unknown. By analyzing 9,328,693 sequencing clones from 393 microbial genomes, we systematically mapped more than 15,000 genes residing in cloning gaps and experimentally showed that their expression products are toxic to the Escherichia coli host. A subset of these toxic sequences was further evaluated through a series of functional assays exploring the mechanisms of their toxicity. Among these genes, our assays revealed novel toxins and restriction enzymes, and new classes of small, non-coding toxic RNAs that reproducibly inhibit E. coli growth. Further analyses also revealed abundant, short, toxic DNA fragments that were predicted to suppress E. coli growth by interacting with the replication initiator DnaA. Our results show that cloning gaps, once considered the result of technical problems, actually serve as a rich source for the discovery of biotechnologically valuable functions, and suggest new modes of antimicrobial interventions. - -\*\*Millman, A. et al. An expanded arsenal of immune systems that protect bacteria from phages. Cell Host Microbe 30, 1556-1569.e5 (2022).\*\* -Bacterial anti-phage systems are frequently clustered in microbial genomes, forming defense islands. This property enabled the recent discovery of multiple defense systems based on their genomic co-localization with known systems, but the full arsenal of anti-phage mechanisms remains unknown. We report the discovery of 21 defense systems that protect bacteria from phages, based on computational genomic analyses and phage-infection experiments. We identified multiple systems with domains involved in eukaryotic antiviral immunity, including those homologous to the ubiquitin-like ISG15 protein, dynamin-like domains, and SEFIR domains, and show their participation in bacterial defenses. Additional systems include domains predicted to manipulate DNA and RNA molecules, alongside toxin-antitoxin systems shown here to function in anti-phage defense. These systems are widely distributed in microbial genomes, and in some bacteria, they form a considerable fraction of the immune arsenal. Our data substantially expand the inventory of defense systems utilized by bacteria to counteract phage infection. - -\*\*Millman, A. et al. An expanded arsenal of immune systems that protect bacteria from phages. Cell Host Microbe 30, 1556-1569.e5 (2022).\*\* -Bacterial anti-phage systems are frequently clustered in microbial genomes, forming defense islands. This property enabled the recent discovery of multiple defense systems based on their genomic co-localization with known systems, but the full arsenal of anti-phage mechanisms remains unknown. We report the discovery of 21 defense systems that protect bacteria from phages, based on computational genomic analyses and phage-infection experiments. We identified multiple systems with domains involved in eukaryotic antiviral immunity, including those homologous to the ubiquitin-like ISG15 protein, dynamin-like domains, and SEFIR domains, and show their participation in bacterial defenses. Additional systems include domains predicted to manipulate DNA and RNA molecules, alongside toxin-antitoxin systems shown here to function in anti-phage defense. These systems are widely distributed in microbial genomes, and in some bacteria, they form a considerable fraction of the immune arsenal. Our data substantially expand the inventory of defense systems utilized by bacteria to counteract phage infection. +::article-doi-list +--- +items: + - 10.1016/j.chom.2022.09.017 + - 10.1016/j.chom.2022.09.017 + - 10.1101/gr.133850.111 +--- +:: diff --git a/content/2.defense-systems/sofic.md b/content/2.defense-systems/sofic.md index 411c97f72815cd17b66515023d71cff4c2d9db20..42caab085f780c1bf6242a5b54396c33a348c06a 100644 --- a/content/2.defense-systems/sofic.md +++ b/content/2.defense-systems/sofic.md @@ -30,6 +30,10 @@ A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage eff ## Relevant abstracts -\*\*Millman, A. et al. An expanded arsenal of immune systems that protect bacteria from phages. Cell Host Microbe 30, 1556-1569.e5 (2022).\*\* -Bacterial anti-phage systems are frequently clustered in microbial genomes, forming defense islands. This property enabled the recent discovery of multiple defense systems based on their genomic co-localization with known systems, but the full arsenal of anti-phage mechanisms remains unknown. We report the discovery of 21 defense systems that protect bacteria from phages, based on computational genomic analyses and phage-infection experiments. We identified multiple systems with domains involved in eukaryotic antiviral immunity, including those homologous to the ubiquitin-like ISG15 protein, dynamin-like domains, and SEFIR domains, and show their participation in bacterial defenses. Additional systems include domains predicted to manipulate DNA and RNA molecules, alongside toxin-antitoxin systems shown here to function in anti-phage defense. These systems are widely distributed in microbial genomes, and in some bacteria, they form a considerable fraction of the immune arsenal. Our data substantially expand the inventory of defense systems utilized by bacteria to counteract phage infection. +::article-doi-list +--- +items: + - 10.1016/j.chom.2022.09.017 +--- +:: diff --git a/content/2.defense-systems/spbk.md b/content/2.defense-systems/spbk.md index 1acf4a458e6d8d6a8bb597584ee91df870067365..3c826c9d2287ae865d983921e3b3197198cc704e 100644 --- a/content/2.defense-systems/spbk.md +++ b/content/2.defense-systems/spbk.md @@ -30,6 +30,10 @@ A system from \*Bacillus subtilis\* in \*Bacillus subtilis\* has an anti-phage e ## Relevant abstracts -\*\*Johnson, C. M., Harden, M. M. & Grossman, A. D. Interactions between mobile genetic elements: An anti-phage gene in an integrative and conjugative element protects host cells from predation by a temperate bacteriophage. PLOS Genetics 18, e1010065 (2022).\*\* -Most bacterial genomes contain horizontally acquired and transmissible mobile genetic elements, including temperate bacteriophages and integrative and conjugative elements. Little is known about how these elements interact and co-evolved as parts of their host genomes. In many cases, it is not known what advantages, if any, these elements provide to their bacterial hosts. Most strains of Bacillus subtilis contain the temperate phage SPß and the integrative and conjugative element ICEBs1. Here we show that the presence of ICEBs1 in cells protects populations of B. subtilis from predation by SPß, likely providing selective pressure for the maintenance of ICEBs1 in B. subtilis. A single gene in ICEBs1 (yddK, now called spbK for SPß killing) was both necessary and sufficient for this protection. spbK inhibited production of SPß, during both activation of a lysogen and following de novo infection. We found that expression spbK, together with the SPß gene yonE constitutes an abortive infection system that leads to cell death. spbK encodes a TIR (Toll-interleukin-1 receptor)-domain protein with similarity to some plant antiviral proteins and animal innate immune signaling proteins. We postulate that many uncharacterized cargo genes in ICEs may confer selective advantage to cells by protecting against other mobile elements. +::article-doi-list +--- +items: + - 10.1371/journal.pgen.1010065 +--- +:: diff --git a/content/2.defense-systems/sspbcde.md b/content/2.defense-systems/sspbcde.md index d085151aa0538fa451b94ef39a2233ee674dba6e..00af2d4e83b455595f0a7f9b357806d128df3058 100644 --- a/content/2.defense-systems/sspbcde.md +++ b/content/2.defense-systems/sspbcde.md @@ -36,9 +36,11 @@ Subsystem SspBCD+SspFGH with a system from \*Vibrio anguillarum\* in \*Escherich ## Relevant abstracts -\*\*Wang, S. et al. SspABCD-SspFGH Constitutes a New Type of DNA Phosphorothioate-Based Bacterial Defense System. mBio 12, e00613-21 (2021).\*\* -Unlike nucleobase modifications in canonical restriction-modification systems, DNA phosphorothioate (PT) epigenetic modification occurs in the DNA sugar-phosphate backbone when the nonbridging oxygen is replaced by sulfur in a double-stranded (ds) or single-stranded (ss) manner governed by DndABCDE or SspABCD, respectively. SspABCD coupled with SspE constitutes a defense barrier in which SspE depends on sequence-specific PT modifications to exert its antiphage activity. Here, we identified a new type of ssDNA PT-based SspABCD-SspFGH defense system capable of providing protection against phages through a mode of action different from that of SspABCD-SspE. We provide further evidence that SspFGH damages non-PT-modified DNA and exerts antiphage activity by suppressing phage DNA replication. Despite their different defense mechanisms, SspFGH and SspE are compatible and pair simultaneously with one SspABCD module, greatly enhancing the protection against phages. Together with the observation that the sspBCD-sspFGH cassette is widely distributed in bacterial genomes, this study highlights the diversity of PT-based defense barriers and expands our knowledge of the arsenal of phage defense mechanisms.IMPORTANCE We recently found that SspABCD, catalyzing single-stranded (ss) DNA phosphorothioate (PT) modification, coupled with SspE provides protection against phage infection. SspE performs both PT-simulated NTPase and DNA-nicking nuclease activities to damage phage DNA, rendering SspA-E a PT-sensing defense system. To our surprise, ssDNA PT modification can also pair with a newly identified 3-gene sspFGH cassette to fend off phage infection with a different mode of action from that of SspE. Interestingly, both SspFGH and SspE can pair with the same SspABCD module for antiphage defense, and their combination provides Escherichia coli JM109 with additive phage resistance up to 105-fold compared to that for either barrier alone. This agrees with our observation that SspFGH and SspE coexist in 36 bacterial genomes, highlighting the diversity of the gene contents and molecular mechanisms of PT-based defense systems. - -\*\*Wang, S. et al. SspABCD-SspFGH Constitutes a New Type of DNA Phosphorothioate-Based Bacterial Defense System. mBio 12, e00613-21 (2021).\*\* -Unlike nucleobase modifications in canonical restriction-modification systems, DNA phosphorothioate (PT) epigenetic modification occurs in the DNA sugar-phosphate backbone when the nonbridging oxygen is replaced by sulfur in a double-stranded (ds) or single-stranded (ss) manner governed by DndABCDE or SspABCD, respectively. SspABCD coupled with SspE constitutes a defense barrier in which SspE depends on sequence-specific PT modifications to exert its antiphage activity. Here, we identified a new type of ssDNA PT-based SspABCD-SspFGH defense system capable of providing protection against phages through a mode of action different from that of SspABCD-SspE. We provide further evidence that SspFGH damages non-PT-modified DNA and exerts antiphage activity by suppressing phage DNA replication. Despite their different defense mechanisms, SspFGH and SspE are compatible and pair simultaneously with one SspABCD module, greatly enhancing the protection against phages. Together with the observation that the sspBCD-sspFGH cassette is widely distributed in bacterial genomes, this study highlights the diversity of PT-based defense barriers and expands our knowledge of the arsenal of phage defense mechanisms.IMPORTANCE We recently found that SspABCD, catalyzing single-stranded (ss) DNA phosphorothioate (PT) modification, coupled with SspE provides protection against phage infection. SspE performs both PT-simulated NTPase and DNA-nicking nuclease activities to damage phage DNA, rendering SspA-E a PT-sensing defense system. To our surprise, ssDNA PT modification can also pair with a newly identified 3-gene sspFGH cassette to fend off phage infection with a different mode of action from that of SspE. Interestingly, both SspFGH and SspE can pair with the same SspABCD module for antiphage defense, and their combination provides Escherichia coli JM109 with additive phage resistance up to 105-fold compared to that for either barrier alone. This agrees with our observation that SspFGH and SspE coexist in 36 bacterial genomes, highlighting the diversity of the gene contents and molecular mechanisms of PT-based defense systems. +::article-doi-list +--- +items: + - 10.1128/mBio.00613-21 + - 10.1128/mBio.00613-21 +--- +:: diff --git a/content/2.defense-systems/stk2.md b/content/2.defense-systems/stk2.md index 3395b504fafaf1de7db1bbdf8973977d0a987a1e..fa6e6e4b9a625f1307f69402568dbf274b1fce32 100644 --- a/content/2.defense-systems/stk2.md +++ b/content/2.defense-systems/stk2.md @@ -41,6 +41,10 @@ A system from \*Staphylococcus epidermidis\* in \*Staphylococcus aureus\* has an ## Relevant abstracts -\*\*Depardieu, F. et al. A Eukaryotic-like Serine/Threonine Kinase Protects Staphylococci against Phages. Cell Host Microbe 20, 471-481 (2016).\*\* -Organisms from all domains of life are infected by viruses. In eukaryotes, serine/threonine kinases play a central role in antiviral response. Bacteria, however, are not commonly known to use protein phosphorylation as part of their defense against phages. Here we identify Stk2, a staphylococcal serine/threonine kinase that provides efficient immunity against bacteriophages by inducing abortive infection. A phage protein of unknown function activates the Stk2 kinase. This leads to the Stk2-dependent phosphorylation of several proteins involved in translation, global transcription control, cell-cycle control, stress response, DNA topology, DNA repair, and central metabolism. Bacterial host cells die as a consequence of Stk2 activation, thereby preventing propagation of the phage to the rest of the bacterial population. Our work shows that mechanisms of viral defense that rely on protein phosphorylation constitute a conserved antiviral strategy across multiple domains of life. +::article-doi-list +--- +items: + - 10.1016/j.chom.2016.08.010 +--- +:: diff --git a/content/2.defense-systems/thoeris.md b/content/2.defense-systems/thoeris.md index 249bba480fa64441493df6f11040f874aad7aa4e..7fbb2559e53ee2c8b4dc7bc83f2f8617c2a8801d 100644 --- a/content/2.defense-systems/thoeris.md +++ b/content/2.defense-systems/thoeris.md @@ -38,9 +38,11 @@ A system from \*Bacillus dafuensis\* in \*Bacillus subtilis\* has an anti-phage ## Relevant abstracts -\*\*Doron, S. et al. Systematic discovery of antiphage defense systems in the microbial pangenome. Science 359, eaar4120 (2018).\*\* -The arms race between bacteria and phages led to the development of sophisticated antiphage defense systems, including CRISPR-Cas and restriction-modification systems. Evidence suggests that known and unknown defense systems are located in "defense islands" in microbial genomes. Here, we comprehensively characterized the bacterial defensive arsenal by examining gene families that are clustered next to known defense genes in prokaryotic genomes. Candidate defense systems were systematically engineered and validated in model bacteria for their antiphage activities. We report nine previously unknown antiphage systems and one antiplasmid system that are widespread in microbes and strongly protect against foreign invaders. These include systems that adopted components of the bacterial flagella and condensin complexes. Our data also suggest a common, ancient ancestry of innate immunity components shared between animals, plants, and bacteria. - -\*\*Ofir, G. et al. Antiviral activity of bacterial TIR domains via immune signalling molecules. Nature 600, 116-120 (2021).\*\* -The Toll/interleukin-1 receptor (TIR) domain is a canonical component of animal and plant immune systems1,2. In plants, intracellular pathogen sensing by immune receptors triggers their TIR domains to generate a molecule that is a variant of cyclic ADP-ribose3,4. This molecule is hypothesized to mediate plant cell death through a pathway that has yet to be resolved5. TIR domains have also been shown to be involved in a bacterial anti-phage defence system called Thoeris6, but the mechanism of Thoeris defence remained unknown. Here we show that phage infection triggers Thoeris TIR-domain proteins to produce an isomer of cyclic ADP-ribose. This molecular signal activates a second protein, ThsA, which then depletes the cell of the essential molecule nicotinamide adenine dinucleotide (NAD) and leads to abortive infection and cell death. We also show that, similar to eukaryotic innate immune systems, bacterial TIR-domain proteins determine the immunological specificity to the invading pathogen. Our results describe an antiviral signalling pathway in bacteria, and suggest that the generation of intracellular signalling molecules is an ancient immunological function of TIR domains that is conserved in both plant and bacterial immunity. +::article-doi-list +--- +items: + - 10.1038/s41586-021-04098-7 + - 10.1126/science.aar4120 +--- +:: diff --git a/content/2.defense-systems/tiamat.md b/content/2.defense-systems/tiamat.md index 98087140c100f22d204fb1a4fc50e7b78c2baa2f..5d3829e47e9e12fcc2c3212143002c6fe8af8a4b 100644 --- a/content/2.defense-systems/tiamat.md +++ b/content/2.defense-systems/tiamat.md @@ -30,6 +30,10 @@ A system from \*Bacillus cereus\* in \*Escherichia coli\* has an anti-phage effe ## Relevant abstracts -\*\*Millman, A. et al. An expanded arsenal of immune systems that protect bacteria from phages. Cell Host Microbe 30, 1556-1569.e5 (2022).\*\* -Bacterial anti-phage systems are frequently clustered in microbial genomes, forming defense islands. This property enabled the recent discovery of multiple defense systems based on their genomic co-localization with known systems, but the full arsenal of anti-phage mechanisms remains unknown. We report the discovery of 21 defense systems that protect bacteria from phages, based on computational genomic analyses and phage-infection experiments. We identified multiple systems with domains involved in eukaryotic antiviral immunity, including those homologous to the ubiquitin-like ISG15 protein, dynamin-like domains, and SEFIR domains, and show their participation in bacterial defenses. Additional systems include domains predicted to manipulate DNA and RNA molecules, alongside toxin-antitoxin systems shown here to function in anti-phage defense. These systems are widely distributed in microbial genomes, and in some bacteria, they form a considerable fraction of the immune arsenal. Our data substantially expand the inventory of defense systems utilized by bacteria to counteract phage infection. +::article-doi-list +--- +items: + - 10.1016/j.chom.2022.09.017 +--- +:: diff --git a/content/2.defense-systems/uzume.md b/content/2.defense-systems/uzume.md index 54ab8592b7ad7fe3ed393fdea631e3fee3ef801c..994e6e65cbc7c5fe80f66334007e4ed711f937cd 100644 --- a/content/2.defense-systems/uzume.md +++ b/content/2.defense-systems/uzume.md @@ -30,6 +30,10 @@ A system from \*Bacillus sp. FJAT-27231\* in \*Bacillus subtilis\* has an anti-p ## Relevant abstracts -\*\*Millman, A. et al. An expanded arsenal of immune systems that protect bacteria from phages. Cell Host Microbe 30, 1556-1569.e5 (2022).\*\* -Bacterial anti-phage systems are frequently clustered in microbial genomes, forming defense islands. This property enabled the recent discovery of multiple defense systems based on their genomic co-localization with known systems, but the full arsenal of anti-phage mechanisms remains unknown. We report the discovery of 21 defense systems that protect bacteria from phages, based on computational genomic analyses and phage-infection experiments. We identified multiple systems with domains involved in eukaryotic antiviral immunity, including those homologous to the ubiquitin-like ISG15 protein, dynamin-like domains, and SEFIR domains, and show their participation in bacterial defenses. Additional systems include domains predicted to manipulate DNA and RNA molecules, alongside toxin-antitoxin systems shown here to function in anti-phage defense. These systems are widely distributed in microbial genomes, and in some bacteria, they form a considerable fraction of the immune arsenal. Our data substantially expand the inventory of defense systems utilized by bacteria to counteract phage infection. +::article-doi-list +--- +items: + - 10.1016/j.chom.2022.09.017 +--- +:: diff --git a/content/2.defense-systems/viperin.md b/content/2.defense-systems/viperin.md index 019daef79b53b3e797b9d295d4ceca5627897538..f803cf5f496cb3d1a11298b17ec8b11a3772f741 100644 --- a/content/2.defense-systems/viperin.md +++ b/content/2.defense-systems/viperin.md @@ -81,6 +81,10 @@ Subsystem pVip63 with a system from \*Pseudoalteromonas sp. XI10\* in \*Escheric ## Relevant abstracts -\*\*Bernheim, A. et al. Prokaryotic viperins produce diverse antiviral molecules. Nature 589, 120-124 (2021).\*\* -Viperin is an interferon-induced cellular protein that is conserved in animals1. It has previously been shown to inhibit the replication of multiple viruses by producing the ribonucleotide 3?-deoxy-3?,4?-didehydro (ddh)-cytidine triphosphate (ddhCTP), which acts as a chain terminator for viral RNA polymerase2. Here we show that eukaryotic viperin originated from a clade of bacterial and archaeal proteins that protect against phage infection. Prokaryotic viperins produce a set of modified ribonucleotides that include ddhCTP, ddh-guanosine triphosphate (ddhGTP) and ddh-uridine triphosphate (ddhUTP). We further show that prokaryotic viperins protect against T7 phage infection by inhibiting viral polymerase-dependent transcription, suggesting that it has an antiviral mechanism of action similar to that of animal viperin. Our results reveal a class of potential natural antiviral compounds produced by bacterial immune systems. +::article-doi-list +--- +items: + - 10.1038/s41586-020-2762-2 +--- +:: diff --git a/content/2.defense-systems/wadjet.md b/content/2.defense-systems/wadjet.md index 26b2740561b03da15dd882f8a17df3a04ee53f48..f4f3664624def76f29074ae05cdd64d9dc46e7f3 100644 --- a/content/2.defense-systems/wadjet.md +++ b/content/2.defense-systems/wadjet.md @@ -32,6 +32,10 @@ Among the 22k complete genomes of RefSeq, this system is present in 2380 genomes ## Relevant abstracts -\*\*Doron, S. et al. Systematic discovery of antiphage defense systems in the microbial pangenome. Science 359, eaar4120 (2018).\*\* -The arms race between bacteria and phages led to the development of sophisticated antiphage defense systems, including CRISPR-Cas and restriction-modification systems. Evidence suggests that known and unknown defense systems are located in "defense islands" in microbial genomes. Here, we comprehensively characterized the bacterial defensive arsenal by examining gene families that are clustered next to known defense genes in prokaryotic genomes. Candidate defense systems were systematically engineered and validated in model bacteria for their antiphage activities. We report nine previously unknown antiphage systems and one antiplasmid system that are widespread in microbes and strongly protect against foreign invaders. These include systems that adopted components of the bacterial flagella and condensin complexes. Our data also suggest a common, ancient ancestry of innate immunity components shared between animals, plants, and bacteria. +::article-doi-list +--- +items: + - 10.1126/science.aar4120 +--- +:: diff --git a/content/2.defense-systems/zorya.md b/content/2.defense-systems/zorya.md index 434103ad3fab8f7f59256727b6f2acc85d2b5ba0..b117473501e72a4a95a6e44dcc3db89fe0f4218f 100644 --- a/content/2.defense-systems/zorya.md +++ b/content/2.defense-systems/zorya.md @@ -38,9 +38,11 @@ Subsystem Type III with a system from \*Stenotrophomonas nitritireducens\* in \* ## Relevant abstracts -\*\*Doron, S. et al. Systematic discovery of antiphage defense systems in the microbial pangenome. Science 359, eaar4120 (2018).\*\* -The arms race between bacteria and phages led to the development of sophisticated antiphage defense systems, including CRISPR-Cas and restriction-modification systems. Evidence suggests that known and unknown defense systems are located in "defense islands" in microbial genomes. Here, we comprehensively characterized the bacterial defensive arsenal by examining gene families that are clustered next to known defense genes in prokaryotic genomes. Candidate defense systems were systematically engineered and validated in model bacteria for their antiphage activities. We report nine previously unknown antiphage systems and one antiplasmid system that are widespread in microbes and strongly protect against foreign invaders. These include systems that adopted components of the bacterial flagella and condensin complexes. Our data also suggest a common, ancient ancestry of innate immunity components shared between animals, plants, and bacteria. - -\*\*Payne, L. J. et al. Identification and classification of antiviral defence systems in bacteria and archaea with PADLOC reveals new system types. Nucleic Acids Research 49, 10868-10878 (2021).\*\* -To provide protection against viral infection and limit the uptake of mobile genetic elements, bacteria and archaea have evolved many diverse defence systems. The discovery and application of CRISPR-Cas adaptive immune systems has spurred recent interest in the identification and classification of new types of defence systems. Many new defence systems have recently been reported but there is a lack of accessible tools available to identify homologs of these systems in different genomes. Here, we report the Prokaryotic Antiviral Defence LOCator (PADLOC), a flexible and scalable open-source tool for defence system identification. With PADLOC, defence system genes are identified using HMM-based homologue searches, followed by validation of system completeness using gene presence/absence and synteny criteria specified by customisable system classifications. We show that PADLOC identifies defence systems with high accuracy and sensitivity. Our modular approach to organising the HMMs and system classifications allows additional defence systems to be easily integrated into the PADLOC database. To demonstrate application of PADLOC to biological questions, we used PADLOC to identify six new subtypes of known defence systems and a putative novel defence system comprised of a helicase, methylase and ATPase. PADLOC is available as a standalone package (https://github.com/padlocbio/padloc) and as a webserver (https://padloc.otago.ac.nz). +::article-doi-list +--- +items: + - 10.1093/nar/gkab883 + - 10.1126/science.aar4120 +--- +::