diff --git a/content/2.defense-systems/old/abi2.md b/content/2.defense-systems/old/abi2.md deleted file mode 100644 index 351668ba0d0859d8cafc802204b3a636c43e579d..0000000000000000000000000000000000000000 --- a/content/2.defense-systems/old/abi2.md +++ /dev/null @@ -1,27 +0,0 @@ ---- -title: Abi2 ---- - -## Example of genomic structure - -The Abi2 system is composed of one protein: Abi_2. - -Here is an example found in the RefSeq database: - - - -Abi2 system in the genome of *Clostridium butyricum* (GCF_014131795.1) is composed of 1 protein: Abi_2 (WP_035763709.1). - -## Distribution of the system among prokaryotes - -The Abi2 system is present in a total of 176 different species. - -Among the 22k complete genomes of RefSeq, this system is present in 1210 genomes (5.3 %). - - - - -*Proportion of genome encoding the Abi2 system for the 14 phyla with more than 50 genomes in the RefSeq database.* - -## Relevant abstracts - diff --git a/content/2.defense-systems/old/abia.md b/content/2.defense-systems/old/abia.md deleted file mode 100644 index c56ceafe0c776277a7c0c0640fb6bed016d6a713..0000000000000000000000000000000000000000 --- a/content/2.defense-systems/old/abia.md +++ /dev/null @@ -1,55 +0,0 @@ -# AbiA - -## Example of genomic structure - -The AbiA system have been describe in a total of 2 subsystems. - -Here is some example found in the RefSeq database: - - - -AbiA_large subsystem in the genome of *Lactobacillus amylovorus* (GCF_002706375.1) is composed of 1 protein: AbiA_large (WP_056940268.1). - - - -AbiA_small subsystem in the genome of *Mesobacillus foraminis* (GCF\_003667765.1) is composed of 2 proteins: AbiA\_small (WP\_121614402.1)and, AbiA\_SLATT (WP\_121614403.1). - -## Distribution of the system among prokaryotes - -The AbiA system is present in a total of 35 different species. - -Among the 22k complete genomes of RefSeq, this system is present in 50 genomes (0.2 %). - - - -*Proportion of genome encoding the AbiA system for the 14 phyla with more than 50 genomes in the RefSeq database.* *Pie chart of the repartition of all the subsystems found in the RefSeq database.* - -## Experimental validation - -AbiA systems were experimentally validated using: - -A system from *lactococcal plasmid* in *lactococci* has an anti-phage effect against 936, c2, P335 (Chopin et al., 2005) - -## Relevant abstracts - - -::article-doi-list ---- -items: - - doi: 10.1016/j.mib.2005.06.006 - - doi: 10.1023/A:1002027321171 - - doi: 10.1093/nar/gkac467 ---- -:: - -<!-- doi: 10.1016/j.mib.2005.06.006 --> - -**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. - diff --git a/content/2.defense-systems/old/abie.md b/content/2.defense-systems/old/abie.md deleted file mode 100644 index 7d9fb3716887ed135d9ac499bc6f2fb3b4f00e63..0000000000000000000000000000000000000000 --- a/content/2.defense-systems/old/abie.md +++ /dev/null @@ -1,54 +0,0 @@ ---- -title: AbiE ---- - -## Description - -AbiE is a family of an anti-phage defense systems. They act through a Toxin-Antitoxin mechanism, and are comprised of a pair of genes, with one gene being toxic while the other confers immunity to this toxicity. - -It is classified as an Abortive infection system. - -## Molecular mechanism - -AbiE systems are encoded by two mandatory genes, abiEi and abiEii (1,2).  The latter encodes for AbiEii, a GTP-binding nucleotidyltransferase (NTase) which expression induce a reversible growth arrest.  On the other hand, abiEi encodes for a AbiEi a transcriptional autorepressor that  binds to the promoter of the abiE operon. - -Based on this mechanisms, AbiE systems are classified as Type IV Toxin-Antitoxin system, where the antitoxin and toxin are both proteins that do not directly interact with each other. - -## Example of genomic structure - -The AbiE system is composed of 2 proteins: AbiEi_1 and, AbiEii. - -Here is an example found in the RefSeq database: - - - - -AbiE system in the genome of *Desulfuromonas versatilis* (GCF\_019704135.1) is composed of 2 proteins: AbiEi\_1 (WP\_221251730.1)and, AbiEii (WP\_221251731.1). - -## Distribution of the system among prokaryotes - -The AbiE system is present in a total of 962 different species. - -Among the 22k complete genomes of RefSeq, this system is present in 3742 genomes (16.4 %). - - - -*Proportion of genome encoding the AbiE system for the 14 phyla with more than 50 genomes in the RefSeq database.* - -## Experimental validation - -AbiE systems were experimentally validated using: - -A system from *lactococcal plasmid* in *lactococci* has an anti-phage effect against 936 (Chopin et al., 2005) - -## 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. - diff --git a/content/2.defense-systems/old/avast.md b/content/2.defense-systems/old/avast.md deleted file mode 100644 index ee472b1412d1a9c73c07db4885ce627cf5927a10..0000000000000000000000000000000000000000 --- a/content/2.defense-systems/old/avast.md +++ /dev/null @@ -1,103 +0,0 @@ ---- -title: AVAST ---- - -## Description -AVAST (antiviral ATPases/NTPases of the STAND superfamily) is a group of anti-phage defense systems, active against some dsDNA phages. - -AVAST systems are composed of NTPases of the STAND (signal transduction ATPases with numerous associated domains) superfamily (1).  STAND-NTPases typically contain a C-terminal helical sensor domain that activates the N-terminal effector domain upon target recognition (1). - -In eukaryotes, STAND-NTPases are associated with programmed cell death, therefore Gao and colleagues hypothesized that AVAST might function through an Abortive infection mechanism. - -## Example of genomic structure - -The AVAST system have been describe in a total of 5 subsystems. - -Here is some example found in the RefSeq database: - - - - -AVAST_I subsystem in the genome of *Vibrio sp.* (GCF\_905175355.1) is composed of 3 proteins: Avs1A (WP\_208445041.1), Avs1B (WP\_208445042.1)and, Avs1C (WP_108173272.1). - - - - -AVAST_II subsystem in the genome of *Escherichia coli* (GCF_018884505.1) is composed of 1 protein: Avs2A (WP_032199984.1). - - - - -AVAST_III subsystem in the genome of *Enterobacter cancerogenus* (GCF_002850575.1) is composed of 2 proteins: Avs3B (WP_199559884.1)and, Avs3A (WP_101737373.1). - - - - -AVAST_IV subsystem in the genome of *Escherichia coli* (GCF_016903595.1) is composed of 1 protein: Avs4A (WP_000240574.1). - - - - -AVAST_V subsystem in the genome of *Leclercia adecarboxylata* (GCF_006171285.1) is composed of 1 protein: Avs5A (WP_139565349.1). - -## Distribution of the system among prokaryotes - -The AVAST system is present in a total of 363 different species. - -Among the 22k complete genomes of RefSeq, this system is present in 1046 genomes (4.6 %). - - - -*Proportion of genome encoding the AVAST system for the 14 phyla with more than 50 genomes in the RefSeq database.* *Pie chart of the repartition of all the subsystems found in the RefSeq database.* - -## Experimental validation - -AVAST systems were experimentally validated using: - -Subsystem SIR2-STAND with a system from *Escherichia fergusonii's PICI (EfCIRHB19-C05)* in *Escherichia coli* has an anti-phage effect against T4, Lambda, HK97, HK544, HK578, T7 (Fillol-Salom et al., 2022) - -Subsystem SIR2-STAND with a system from *Escherichia fergusonii's PICI (EfCIRHB19-C05)* in *Salmonella enterica * has an anti-phage effect against P22, BTP1, ES18, det7 (Fillol-Salom et al., 2022) - -Subsystem SIR2-STAND with a system from *Escherichia fergusonii's PICI (EfCIRHB19-C05)* in *Klebsiella pneumoniae * has an anti-phage effect against Pokey (Fillol-Salom et al., 2022) - -Subsystem Metallo beta-lactamase + protease + STAND (Type 1) with a system from *Erwinia piriflorinigrans* in *Escherichia coli* has an anti-phage effect against P1 (Gao et al., 2020) - -Subsystem STAND (Type 2) with a system from *Escherichia coli* in *Escherichia coli* has an anti-phage effect against T4, P1 (Gao et al., 2020) - -Subsystem DUF4297-STAND (Type 3) with a system from *Salmonella enterica* in *Escherichia coli* has an anti-phage effect against T2, T3, T7, PhiV-1 (Gao et al., 2020) - -Subsystem Mrr-STAND (Type 4) with a system from *Escherichia coli* in *Escherichia coli* has an anti-phage effect against T3, T7, PhiV-1 (Gao et al., 2020) - -Subsystem SIR2-STAND (Type 5) with a system from *Escherichia coli* in *Escherichia coli* has an anti-phage effect against T2 (Gao et al., 2020) - -Subsystem SeAvs1 with a system from *Salmonella enterica* in *Escherichia coli* has an anti-phage effect against P1, ZL-19 (Gao et al., 2022) - -Subsystem EcAcs1 with a system from *Escherichia coli* in *Escherichia coli* has an anti-phage effect against ZL-19 (Gao et al., 2022) - -Subsystem EpAvs1 with a system from *Erwinia piriflorinigrans* in *Escherichia coli* has an anti-phage effect against P1, Lambda, , ZL-19 (Gao et al., 2022) - -Subsystem SeAvs3 with a system from *Salmonella enterica* in *Escherichia coli* has an anti-phage effect against T7, PhiV-1, ZL-19 (Gao et al., 2022) - -Subsystem KvAvs3 with a system from *Klebsiella variicola* in *Escherichia coli* has an anti-phage effect against P1, ZL-19 (Gao et al., 2022) - -Subsystem EcAvs2 with a system from *Escherichia coli* in *Escherichia coli* has an anti-phage effect against T7, PhiV-1, P1, T4, T5, ZL-19 (Gao et al., 2022) - -Subsystem Ec2Avs2 with a system from *Escherichia coli* in *Escherichia coli* has an anti-phage effect against P1 (Gao et al., 2022) - -Subsystem EcAvs4 with a system from *Escherichia coli* in *Escherichia coli* has an anti-phage effect against T7, PhiV-1, ZL-19 (Gao et al., 2022) - -Subsystem Ec2Avs4 with a system from *Escherichia coli* in *Escherichia coli* has an anti-phage effect against T7, PhiV-1, ZL-19 (Gao et al., 2022) - -Subsystem KpAvs4 with a system from *Klebsiella pneumoniae* in *Escherichia coli* has an anti-phage effect against ZL-19 (Gao et al., 2022) - -Subsystem CcAvs4 with a system from *Corallococcus coralloides* in *Escherichia coli* has an anti-phage effect against T7 (Gao et al., 2022) - -## Relevant abstracts - -::article-doi-list ---- -items: - - doi: 10.1126/science.abm4096 - - doi: 10.1126/science.aba0372 ---- -:: \ No newline at end of file diff --git a/content/2.defense-systems/old/gao_rl.md b/content/2.defense-systems/old/gao_rl.md deleted file mode 100644 index 04853174ba633c1f5960badcd5e2f803cc39dabb..0000000000000000000000000000000000000000 --- a/content/2.defense-systems/old/gao_rl.md +++ /dev/null @@ -1,33 +0,0 @@ -# Gao\_RL - -## Example of genomic structure - -The Gao\_RL system is composed of 4 proteins: RL\_D, RL\_C, RL\_B and, RL\_A. - -Here is an example found in the RefSeq database: - - - -Gao\\_RL system in the genome of \*Morganella morganii\* (GCF\\_020790175.1) is composed of 4 proteins: RL\\_D (WP\\_064483389.1), RL\\_C (WP\\_064483388.1), RL\\_B (WP\\_064483387.1)and, RL\\_A (WP\\_064483386.1). - -## Distribution of the system among prokaryotes - -The Gao\_RL system is present in a total of 77 different species. - -Among the 22k complete genomes of RefSeq, this system is present in 133 genomes (0.6 %). - - - -\*Proportion of genome encoding the Gao\_RL system for the 14 phyla with more than 50 genomes in the RefSeq database.\* - -## Experimental validation - -Gao\_RL systems were experimentally validated using: - -A system from \*Escherichia coli\* in \*Escherichia coli\* has an anti-phage effect against P1, Lambda, M13 (Gao et al., 2020) - -## 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. - diff --git a/content/2.defense-systems/old/paris.md b/content/2.defense-systems/old/paris.md deleted file mode 100644 index eb31bf0e54e2f286b273fbf8a4e286223a483407..0000000000000000000000000000000000000000 --- a/content/2.defense-systems/old/paris.md +++ /dev/null @@ -1,60 +0,0 @@ ---- -title: Paris -toc: true -layout: article ---- - -# PARIS system - -PARIS (for Phage Anti-Restriction-Induced System) is a novel anti-phage system. PARIS is found in 4% of prokaryotic genomes. It comprises an ATPase associated with a DUF4435 protein, which can be found either as a two-gene cassette or a single-gene fusion (1). - -This system relies on an unknown Abortive infection mechanism to trigger growth arrest upon sensing a phage-encoded protein (Ocr). Interestingly, the Ocr protein has been found to inhibit R-M systems and BREX systems, making PARIS a suitable defense mechanism against RM resistant and/or BREX resistant phages (1, 2, 3). - -## Relevant abstracts - -**François Rousset, Julien Dowding, Aude Bernheim, Eduardo P.C. Rocha, David Bikard, Prophage-encoded hotspots of bacterial immune systems, bioRxiv 2021.01.21.427644; doi: https://doi.org/10.1101/2021.01.21.427644** - -The arms race between bacteria and phages led to the emergence of a variety of genetic systems used by bacteria to defend against viral infection, some of which were repurposed as powerful biotechnological tools. While numerous defense systems have been identified in genomic regions termed defense islands, it is believed that many more remain to be discovered. Here, we show that P2- like prophages and their P4-like satellites have genomic hotspots that represent a significant source of novel anti-phage systems. We validate the defense activity of 14 systems spanning various protein domains and describe PARIS, an abortive infection system triggered by a phage-encoded anti-restriction protein. Immunity hotspots are present across prophages of distant bacterial species, highlighting their biological importance in the competition between bacteria and phages. - -## Example of genomic structure - -There is 2 types of PARIS systems: - -### Paris type I - -Paris type I : AriA*I  (AAA*15) + AriB (DUF4435) or AriAB (fused AAA_15 + DUF4435) - - - -<br/> - -Paris type I system in _Salmonella enterica_ (GCF\__000006945.2). AriA_I:_ NP_461673.1; AriB: NP_461674.1 - - - -<br/> - -Paris type I merge system in _Sideroxydans lithotrophicus_ (GCF\__000025705.1). AriAB_I:_ WP_013030315.1 - -### Paris type II - -2\. Paris type II : AriAB (AAA\__21) + AriB (DUF4435) or AriAB (fused AAA_21 + DUF4435)_ - - - -Paris type II system in *Escherichia coli* (GCF_000026245.1*). AriA_II:* WP_000190961.1 ; AriB: WP_000134255.1 - - - -Paris type II merge system in _Desulfovibrio desulfuricans_ (GCF\__000025705.1). AriAB_I:_ WP_209818471.1 - -## References - -::article-doi-list ---- -items: - - doi: 10.1101/2021.01.21.427644 - - doi: 10.1093/nar/gkaa290 - - doi: 10.1016/0022-2836(75)90083-2 ---- -:: \ No newline at end of file diff --git a/content/2.defense-systems/old/rm.md b/content/2.defense-systems/old/rm.md deleted file mode 100644 index 8855525f9ade6b966b483c7e88bf297eb2e7fe5f..0000000000000000000000000000000000000000 --- a/content/2.defense-systems/old/rm.md +++ /dev/null @@ -1,43 +0,0 @@ -# RM - -## Example of genomic structure - -The RM system have been describe in a total of 5 subsystems. - -Here is some example found in the RefSeq database: - -<img src="./data/RM_Type_I.svg"> - -RM\_Type\_I subsystem in the genome of *Aeromonas veronii* (GCF\_014169835.1) is composed of 4 proteins: Type\_I\_MTases (WP\_182963881.1), Type\_I\_MTases (WP\_182963881.1), Type\_I\_S (WP\_182963883.1)and, Type\_I\_REases (WP\_182963884.1). - -<img src="./data/RM_Type_II.svg"> - -RM\_Type\_II subsystem in the genome of *Mannheimia haemolytica* (GCF\_007965905.1) is composed of 2 proteins: Type\_II\_MTases (WP\_006248352.1)and, Type\_II\_REases (WP\_006253295.1). - -<img src="./data/RM_Type_IIG.svg"> - -RM\_Type\_IIG subsystem in the genome of *Spirochaeta africana* (GCF\_000242595.2) is composed of 1 protein: Type\_IIG (WP\_014455422.1). - -<img src="./data/RM_Type_III.svg"> - -RM\_Type\_III subsystem in the genome of *Pannonibacter phragmitetus* (GCF\_001484065.1) is composed of 2 proteins: Type\_III\_MTases (WP\_058898889.1)and, Type\_III\_REases (WP\_058898890.1). - -<img src="./data/RM_Type_IV.svg"> - -RM\_Type\_IV subsystem in the genome of *Clostridioides difficile* (GCF\_018884605.1) is composed of 1 protein: Type\_IV\_REases (WP\_021364579.1). - -## Distribution of the system among prokaryotes - -The RM system is present in a total of 4699 different species. - -Among the 22k complete genomes of RefSeq, this system is present in 19087 genomes (83.7 %). - -<img src="./data/Distribution_RM.svg" max-width=800px> - -*Proportion of genome encoding the RM system for the 14 phyla with more than 50 genomes in the RefSeq database.* *Pie chart of the repartition of all the subsystems found in the RefSeq database.* - -## 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. - diff --git a/content/2.defense-systems/old/viperin.md b/content/2.defense-systems/old/viperin.md deleted file mode 100644 index bf468f346510958814441f3a019afd8cfec568bc..0000000000000000000000000000000000000000 --- a/content/2.defense-systems/old/viperin.md +++ /dev/null @@ -1,87 +0,0 @@ ---- -title: Viperin -layout: article ---- - -## Description - -Viperins, for “Virus Inhibitory Protein, Endoplasmic Reticulum-associated, INterferon-inducibleâ€, are antiviral enzymes whose expression is stimulated by interferons in eukaryotic cells. They are important components of eukaryotic innate immunity, and present antiviral activity against a wide diversity of viruses, including double-stranded DNA viruses, single-strand RNA viruses and retroviruses (1). - -Recently, Viperin-like enzymes were found in prokaryotes (pVips). Strikingly, like their eukaryotic counter-part with eukaryotic viruses, pVips provide clear protection against phage infection to their host, and therefore constitute a new defense system (2). Like eukaryotic Viperins, pVips produce modified nucleotides that block phage transcription, acting as chain terminators. They constitute a form of chemical defense. A recent study reported that pVips can be found in around 0.5% of prokaryotic genomes (3). - -## Molecular mechanism - - -Fig.1: Catalytic activity of human Viperin generates ddhCTP (Ebrahimi et al. al., 2020) - -Viperins are members of the radical S-adenosylmethionine (rSAM) superfamily. This group of enzymes use a \[4Fe-4S\] cluster to cleave S-adenosylmethionine (SAM) reductively, generating a radical which is generally transferred to a substrate. It was demonstrated that through their \[4Fe-4S\] cluster catalytic activity, eukaryotic viperins convert a ribonucleotide, the cytidine triphosphate (CTP) into a modified ribonucleotide, the 3′-deoxy-3′,4′-didehydro-CTP (ddhCTP) (4,5). - -Prokaryotic Viperins also convert ribonucleotides triphosphate into modified ribonucleotides, but contrary to their eukaryotic counterparts can use a diversity of substrates to produce ddhCTP, or ddh-guanosine triphosphate (ddhGTP), or ddh-uridine triphosphate (ddhUTP), or several of these nucleotides for certain pVips (2). - -Compared to the initial ribonucleotide triphosphate, the modified ddh-nucleotide product of Viperins lacks a hydroxyl group at the 3′ carbon of the ribose (Fig.1). The ddh-nucleotides produced by Viperins can be used as substrates by some viral RNA polymerases. Because of their lost hydroxyl group at the 3’carbon of the ribose, once incorporated into the newly forming viral RNA chain, these ddh-nucleotides act as chain terminators. By preventing further polymerization of the viral RNA chain, ddh-nucleotides can inhibit viral replication (2,4,5). - -## Example of genomic structure - -The Viperin system is composed of one protein: pVip. - -Here is an example found in the RefSeq database: - -<img src="./data/Viperin.svg"> - -Viperin system in the genome of *Moritella yayanosii* is composed of 1 protein: pVip (WP\_112711942.1). - -## Distribution of the system among prokaryotes - -The Viperin system is present in a total of 85 different species. - -Among the 22k complete genomes of RefSeq, this system is present in 118 genomes (0.5 %). - -<img src="./data/Distribution_Viperin.svg" max-width=800px> - -*Proportion of genome encoding the Viperin system for the 14 phyla with more than 50 genomes in the RefSeq database.* - -## Experimental validation - -Viperin systems were experimentally validated using: - -Subsystem pVip6 with a system from *Selenomonas ruminatium* in *Escherichia coli* has an anti-phage effect against T7 (Bernheim et al., 2020) - -Subsystem pVip7 with a system from *Fibrobacter sp. UWT3* in *Escherichia coli* has an anti-phage effect against T7 (Bernheim et al., 2020) - -Subsystem pVip9 with a system from *Vibrio porteresiae* in *Escherichia coli* has an anti-phage effect against T7 (Bernheim et al., 2020) - -Subsystem pVip12 with a system from *Ruegeria intermedia* in *Escherichia coli* has an anti-phage effect against T7 (Bernheim et al., 2020) - -Subsystem pVip15 with a system from *Coraliomargarita akajimensis* in *Escherichia coli* has an anti-phage effect against T7 (Bernheim et al., 2020) - -Subsystem pVip21 with a system from *Lewinella persica* in *Escherichia coli* has an anti-phage effect against T7 (Bernheim et al., 2020) - -Subsystem pVip32 with a system from *Phormidium sp. OSCR GFM* in *Escherichia coli* has an anti-phage effect against T7 (Bernheim et al., 2020) - -Subsystem pVip34 with a system from *Cryomorphaceae bacterium* in *Escherichia coli* has an anti-phage effect against T7 (Bernheim et al., 2020) - -Subsystem pVip37 with a system from *Shewanella sp. cp20* in *Escherichia coli* has an anti-phage effect against T7 (Bernheim et al., 2020) - -Subsystem pVip39 with a system from *Burkholderiales-76 (UID4002)* in *Escherichia coli* has an anti-phage effect against T7 (Bernheim et al., 2020) - -Subsystem pVip44 with a system from *Chondromyces crocatus* in *Escherichia coli* has an anti-phage effect against T7 (Bernheim et al., 2020) - -Subsystem pVip46 with a system from *Photobacterium swingsii* in *Escherichia coli* has an anti-phage effect against T7 (Bernheim et al., 2020) - -Subsystem pVip57 with a system from *Flavobacterium lacus* in *Escherichia coli* has an anti-phage effect against T7 (Bernheim et al., 2020) - -Subsystem pVip58 with a system from *Pseudoalteromonas ulvae* in *Escherichia coli* has an anti-phage effect against T7 (Bernheim et al., 2020) - -Subsystem pVip60 with a system from *Lacinutrix sp. JCM 13824* in *Escherichia coli* has an anti-phage effect against T7 (Bernheim et al., 2020) - -Subsystem pVip61 with a system from *Euryarchaeota archaeon SCGC AG-487_M08* in *Escherichia coli* has an anti-phage effect against T7 (Bernheim et al., 2020) - -Subsystem pVip62 with a system from *Fibrobacteria bacterium* in *Escherichia coli* has an anti-phage effect against T7 (Bernheim et al., 2020) - -Subsystem pVip63 with a system from *Pseudoalteromonas sp. XI10* in *Escherichia coli* has an anti-phage effect against T7 (Bernheim et al., 2020) - -## 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. -