From bc1d3446f504bf6b82a3f9855ab28c7abdca2573 Mon Sep 17 00:00:00 2001 From: jeanrjc <jean.cury@normalesup.org> Date: Thu, 14 Sep 2023 17:59:10 +0200 Subject: [PATCH] Modify reference with doi plugin (really this time) --- content/2.defense-systems/abia.md | 16 +++++------ content/2.defense-systems/abib.md | 12 ++++---- content/2.defense-systems/abic.md | 12 ++++---- content/2.defense-systems/abid.md | 12 ++++---- content/2.defense-systems/abie.md | 16 +++++------ content/2.defense-systems/abig.md | 12 ++++---- content/2.defense-systems/abih.md | 16 +++++------ content/2.defense-systems/abii.md | 12 ++++---- content/2.defense-systems/abij.md | 12 ++++---- content/2.defense-systems/abik.md | 16 +++++------ content/2.defense-systems/abil.md | 12 ++++---- content/2.defense-systems/abin.md | 12 ++++---- content/2.defense-systems/abio.md | 12 ++++---- content/2.defense-systems/abip2.md | 16 +++++------ content/2.defense-systems/abiq.md | 16 +++++------ content/2.defense-systems/abir.md | 12 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| 8 ++++-- content/2.defense-systems/wadjet.md | 8 ++++-- content/2.defense-systems/zorya.md | 12 ++++---- 119 files changed, 774 insertions(+), 405 deletions(-) diff --git a/content/2.defense-systems/abia.md b/content/2.defense-systems/abia.md index a212c326..330be5b1 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 a2157297..bc399c55 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 67b6d493..8cf4a7dc 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 b883f7c5..94d81ae8 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 ce2f4bca..08281992 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 1b3b780b..6212ea72 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 185e7e7a..390f36ef 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 05ce9206..74dccabc 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 198f32cc..e11da1a3 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 839f449b..e54df0e1 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 983f8780..48bc2166 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 1931a637..ea2c042b 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 66224af7..377fb61e 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 6dff3b8b..c51303e9 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 aea83f82..14cd8c8c 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 ffc6c775..03fbabdd 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 6ce67e66..54cedcc9 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 aff2ae21..43cb5dbb 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 22ebf6bc..89db7fa2 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 09dde3ef..78081068 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 60a83fe4..bb174371 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 80912d7c..adb0fc47 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 7f73642c..b8c75a27 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 69f97328..6ec5f4c1 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 fa713137..94ec25e4 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 0bca0ef5..09a20ef8 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 69f33f63..2f934137 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 6b12aca8..ed1da650 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 850fd7d0..49403373 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 dbb35e95..b881eac7 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 d40f876b..b5a7aeb8 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 e83d0ec7..3c077fd8 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 64d04e46..b886a21c 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 c364e249..c3604004 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 6061cc1a..0d58f9dd 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 3f11fb80..4b93d5cb 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 c97fc8f8..59d0afa2 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 28a137ee..7b35c9cb 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 d9778bd2..37674c2f 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 9be97955..dab338df 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 b0148c85..dae5c35b 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 7d0298c2..3ac030b0 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 f15521a0..ddef56f4 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 9fb5adbb..6e0fe35c 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 e9e294c8..8da2536c 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 445d8982..17be4cc5 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 f73ed4b9..59868acc 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 034601b5..dac746a4 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 97f64384..53311528 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 7b691e8b..ad91d33d 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 6756f417..f6ff2758 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 34c54eed..d97a5221 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 869a5a82..9f7e24fa 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 3665df56..d00ef02a 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 24ebd95d..e6059e93 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 e2e5d850..d5b1dffe 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 210145d6..6c8d680c 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 c013ad98..89d44115 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 aebf20b5..f562ef04 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 a291e8c2..1652fa61 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 b1c51cef..a40033ee 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 a67939bc..8a2596d3 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 7ef10522..7ef26b38 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 ce339df7..c9dffa18 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 357b423b..823c9d05 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 adb7c4b4..514e03ba 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 8867540a..23c5735e 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 6fb99343..caea84c1 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 e44331b9..1ff6bd29 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 b31b5406..797d8817 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 84fff571..1e25c4d2 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 a9dd4cea..97107779 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 5719c580..51ff20ad 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 3011a645..d374dd09 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 4a42a0ca..68a83f0a 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 d1e1757b..d3b03c61 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 140fa426..59d05aa1 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 a8a92fa5..39e5cb8f 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 15b65704..eff24099 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 71ec5092..475c805d 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 e495e428..5acbdaac 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 85cce53e..c41d865f 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 6cb9f2f0..254a02f4 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 673b2824..2e5e95bf 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 49af4ee2..ba062723 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 e0effbc2..5f8155e9 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 245bfc89..ebbec7c7 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 6f57554b..1ce9dea5 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 152dad50..3bc102d2 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 484c3098..196eb31d 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 c9cd89b2..65a83b95 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 f46c6900..90b98180 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 c23cf8e5..68367c6d 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 7a4392c5..58ec8aab 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 a79f672c..bd38e210 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 d9d81ccd..d68025da 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 64af1fa2..0d27a2c4 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 f255acc9..b74e9936 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 f86d4631..7ca091d6 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 6c421e94..20e9852e 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 0a8b8020..55374a76 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 002c33ef..a03da922 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 283184b5..52efa098 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 21fe821d..cd3a5a9f 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 76bfa9d1..74ebbafc 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 475c57be..2b676b22 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 954030e4..2bb5aa9a 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 6eb32679..144dced8 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 a9a4fe5b..8c477503 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 411c97f7..42caab08 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 1acf4a45..3c826c9d 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 d085151a..00af2d4e 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 3395b504..fa6e6e4b 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 249bba48..7fbb2559 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 98087140..5d3829e4 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 54ab8592..994e6e65 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 019daef7..f803cf5f 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 26b27405..f4f36646 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 434103ad..b1174735 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 +--- +:: -- GitLab