diff --git a/.gitlab-ci.yml b/.gitlab-ci.yml
index d34e465495e79b9a24e2130163e707d2a3d8426f..61cb15267bc4f0cf3ebbdf12f3fb2e1935b20043 100644
--- a/.gitlab-ci.yml
+++ b/.gitlab-ci.yml
@@ -197,6 +197,12 @@ lint:
variables:
MEILI_HOST: "http://localhost:7700"
script:
+ - >
+ df-wiki-cli
+ content systems
+ --dir content/3.defense-systems/
+ --pfam public/pfam-a-hmm.csv
+ --output data/list-systems.json
- >
df-wiki-cli
meilisearch
diff --git a/content/3.defense-systems/butters_gp30_gp31.md b/content/3.defense-systems/butters_gp30_gp31.md
index 1e2afd9633c0b3ca4d7681c38a43a38b19da039d..cf8c7195e32cc3b78a29a6e078708de8d8181f74 100644
--- a/content/3.defense-systems/butters_gp30_gp31.md
+++ b/content/3.defense-systems/butters_gp30_gp31.md
@@ -9,7 +9,7 @@ tableColumns:
Sensor: Unknown
Activator: Unknown
Effector: Unknown
- PFAM:
+ PFAM: ''
contributors:
- Helena Shomar
- Marie Guillaume
diff --git a/data/list-systems.json b/data/list-systems.json
index a25f4c9c6949eb14eab8ea85deaec1451a3bafa3..69f86a8f638506ce8f742ab7174c97e245d50c27 100644
--- a/data/list-systems.json
+++ b/data/list-systems.json
@@ -5248,4 +5248,5412 @@
}
]
}
+][
+ {
+ "title": "Butters_gp30_gp31",
+ "contributors": [
+ "Helena Shomar",
+ "Marie Guillaume"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1128/mSystems.00534-20"
+ }
+ ],
+ "doi": "10.1128/mSystems.00534-20",
+ "abstract": "Many sequenced bacterial genomes, including those of pathogenic bacteria, contain prophages. Some prophages encode defense systems that protect their bacterial host against heterotypic viral attack. Understanding the mechanisms undergirding these defense systems is crucial to appreciate the scope of bacterial immunity against viral infections and will be critical for better implementation of phage therapy that would require evasion of these defenses. Furthermore, such knowledge of prophage-encoded defense mechanisms may be useful for developing novel genetic tools for engineering phage-resistant bacteria of industrial importance., A diverse set of prophage-mediated mechanisms protecting bacterial hosts from infection has been recently uncovered within cluster N mycobacteriophages isolated on the host, Mycobacterium smegmatis mc2155. In that context, we unveil a novel defense mechanism in cluster N prophage Butters. By using bioinformatics analyses, phage plating efficiency experiments, microscopy, and immunoprecipitation assays, we show that Butters genes located in the central region of the genome play a key role in the defense against heterotypic viral attack. Our study suggests that a two-component system, articulated by interactions between protein products of genes 30 and 31, confers defense against heterotypic phage infection by PurpleHaze (cluster A/subcluster A3) or Alma (cluster A/subcluster A9) but is insufficient to confer defense against attack by the heterotypic phage Island3 (cluster I/subcluster I1). Therefore, based on heterotypic phage plating efficiencies on the Butters lysogen, additional prophage genes required for defense are implicated and further show specificity of prophage-encoded defense systems., IMPORTANCE Many sequenced bacterial genomes, including those of pathogenic bacteria, contain prophages. Some prophages encode defense systems that protect their bacterial host against heterotypic viral attack. Understanding the mechanisms undergirding these defense systems is crucial to appreciate the scope of bacterial immunity against viral infections and will be critical for better implementation of phage therapy that would require evasion of these defenses. Furthermore, such knowledge of prophage-encoded defense mechanisms may be useful for developing novel genetic tools for engineering phage-resistant bacteria of industrial importance.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": []
+ },
+ {
+ "title": "RloC",
+ "doi": "10.1111/j.1365-2958.2008.06387.x",
+ "abstract": "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.\n",
+ "Sensor": "Monitor the integrity of the bacterial cell machinery",
+ "Activator": "Unknown",
+ "Effector": "Nucleic acid degrading",
+ "PFAM": [
+ {
+ "ID": "AAA_13",
+ "DE": "AAA domain",
+ "GA": "36; 36;",
+ "TP": "Domain",
+ "ML": 714,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13166"
+ }
+ ]
+ },
+ {
+ "title": "Dpd",
+ "doi": "10.1073/pnas.1518570113",
+ "abstract": "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 2\u2019-deoxy-preQ0 and 2\u2019-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, 2\u2019-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.\n",
+ "PFAM": [
+ {
+ "ID": "SNF2-rel_dom",
+ "DE": "SNF2-related domain",
+ "GA": "23.9; 23.9;",
+ "TP": "Domain",
+ "ML": 290,
+ "CL": "CL0023",
+ "NE": "Bromodomain",
+ "AC": "PF00176"
+ },
+ {
+ "ID": "DEAD",
+ "DE": "DEAD/DEAH box helicase",
+ "GA": "26; 24.1;",
+ "TP": "Domain",
+ "ML": 166,
+ "CL": "CL0023",
+ "NE": "SPRY",
+ "AC": "PF00270"
+ },
+ {
+ "ID": "Helicase_C",
+ "DE": "Helicase conserved C-terminal domain",
+ "GA": "23.5; 23.5;",
+ "TP": "Domain",
+ "ML": 110,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF00271"
+ },
+ {
+ "ID": "GTP_cyclohydroI",
+ "DE": "GTP cyclohydrolase I",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 179,
+ "CL": "CL0334",
+ "NE": "",
+ "AC": "PF01227"
+ },
+ {
+ "ID": "PTPS",
+ "DE": "6-pyruvoyl tetrahydropterin synthase",
+ "GA": "22.4; 22.4;",
+ "TP": "Domain",
+ "ML": 121,
+ "CL": "CL0334",
+ "NE": "",
+ "AC": "PF01242"
+ },
+ {
+ "ID": "Radical_SAM",
+ "DE": "Radical SAM superfamily",
+ "GA": "29.5; 29.5;",
+ "TP": "Domain",
+ "ML": 167,
+ "CL": "CL0036",
+ "NE": "Fer4",
+ "AC": "PF04055"
+ },
+ {
+ "ID": "ResIII",
+ "DE": "Type III restriction enzyme, res subunit",
+ "GA": "22.5; 22.5;",
+ "TP": "Family",
+ "ML": 164,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF04851"
+ },
+ {
+ "ID": "QueC",
+ "DE": "Queuosine biosynthesis protein QueC",
+ "GA": "22; 22;",
+ "TP": "Domain",
+ "ML": 210,
+ "CL": "CL0039",
+ "NE": "",
+ "AC": "PF06508"
+ },
+ {
+ "ID": "PLDc_2",
+ "DE": "PLD-like domain",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 132,
+ "CL": "CL0479",
+ "NE": "",
+ "AC": "PF13091"
+ },
+ {
+ "ID": "Fer4_12",
+ "DE": "4Fe-4S single cluster domain",
+ "GA": "22; 22;",
+ "TP": "Domain",
+ "ML": 137,
+ "CL": "CL0344",
+ "NE": "",
+ "AC": "PF13353"
+ },
+ {
+ "ID": "DndB",
+ "DE": "DNA-sulfur modification-associated",
+ "GA": "29.1; 29.1;",
+ "TP": "Family",
+ "ML": 339,
+ "CL": "",
+ "NE": "",
+ "AC": "PF14072"
+ }
+ ]
+ },
+ {
+ "title": "AbiE",
+ "doi": "10.1016/j.mib.2005.06.006",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "AbiEii",
+ "DE": "Nucleotidyl transferase AbiEii toxin, Type IV TA system",
+ "GA": "22.5; 22.5;",
+ "TP": "Domain",
+ "ML": 238,
+ "CL": "CL0260",
+ "NE": "",
+ "AC": "PF08843"
+ },
+ {
+ "ID": "AbiEi_1",
+ "DE": "AbiEi antitoxin C-terminal domain",
+ "GA": "22.2; 22.2;",
+ "TP": "Domain",
+ "ML": 143,
+ "CL": "CL0578",
+ "NE": "",
+ "AC": "PF09407"
+ },
+ {
+ "ID": "AbiEi_2",
+ "DE": "Transcriptional regulator, AbiEi antitoxin, Type IV TA system",
+ "GA": "21; 21;",
+ "TP": "Family",
+ "ML": 143,
+ "CL": "CL0578",
+ "NE": "",
+ "AC": "PF09952"
+ },
+ {
+ "ID": "AbiEi_3",
+ "DE": "Transcriptional regulator, AbiEi antitoxin, Type IV TA system",
+ "GA": "26; 26;",
+ "TP": "Family",
+ "ML": 157,
+ "CL": "CL0578",
+ "NE": "",
+ "AC": "PF11459"
+ },
+ {
+ "ID": "AbiEi_4",
+ "DE": "Transcriptional regulator, AbiEi antitoxin",
+ "GA": "25; 25;",
+ "TP": "Domain",
+ "ML": 49,
+ "CL": "CL0123",
+ "NE": "",
+ "AC": "PF13338"
+ },
+ {
+ "ID": "AbiEi_3_N",
+ "DE": "Transcriptional regulator, AbiEi antitoxin N-terminal domain",
+ "GA": "26; 26;",
+ "TP": "Domain",
+ "ML": 93,
+ "CL": "CL0123",
+ "NE": "",
+ "AC": "PF17194"
+ }
+ ]
+ },
+ {
+ "title": "Lamassu-Fam",
+ "contributors": [
+ "Matthieu Haudiquet",
+ "Aude Bernheim"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1126/science.aar4120"
+ },
+ {
+ "doi": "10.1016/j.chom.2022.09.017"
+ },
+ {
+ "doi": "10.1093/nar/gkab883"
+ },
+ {
+ "doi": "10.1038/s41586-022-04546-y"
+ },
+ {
+ "doi": "10.1101/2022.11.18.517080"
+ }
+ ],
+ "doi": "10.1016/j.chom.2022.09.017",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Diverse (Nucleic acid degrading (?), Nucleotide modifying (?), Membrane disrupting (?))",
+ "PFAM": [
+ {
+ "ID": "Lactamase_B",
+ "DE": "Metallo-beta-lactamase superfamily",
+ "GA": "22.7; 21.9;",
+ "TP": "Domain",
+ "ML": 196,
+ "CL": "CL0381",
+ "NE": "",
+ "AC": "PF00753"
+ },
+ {
+ "ID": "SMC_N",
+ "DE": "RecF/RecN/SMC N terminal domain",
+ "GA": "40; 40;",
+ "TP": "Domain",
+ "ML": 220,
+ "CL": "CL0023",
+ "NE": "SMC_hinge",
+ "AC": "PF02463"
+ },
+ {
+ "ID": "DUF676",
+ "DE": "Putative serine esterase (DUF676)",
+ "GA": "20.3; 20.3;",
+ "TP": "Family",
+ "ML": 217,
+ "CL": "CL0028",
+ "NE": "",
+ "AC": "PF05057"
+ },
+ {
+ "ID": "DUF3732",
+ "DE": "Protein of unknown function (DUF3732)",
+ "GA": "25; 25;",
+ "TP": "Family",
+ "ML": 185,
+ "CL": "",
+ "NE": "",
+ "AC": "PF12532"
+ },
+ {
+ "ID": "AAA_15",
+ "DE": "AAA ATPase domain",
+ "GA": "32.1; 32.1;",
+ "TP": "Domain",
+ "ML": 399,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13175"
+ },
+ {
+ "ID": "SIR2_2",
+ "DE": "SIR2-like domain",
+ "GA": "24.5; 24.5;",
+ "TP": "Family",
+ "ML": 142,
+ "CL": "CL0063",
+ "NE": "",
+ "AC": "PF13289"
+ },
+ {
+ "ID": "AAA_23",
+ "DE": "AAA domain",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 201,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13476"
+ },
+ {
+ "ID": "Cap4_nuclease",
+ "DE": "Cap4, dsDNA endonuclease domain",
+ "GA": "26.2; 26.2;",
+ "TP": "Family",
+ "ML": 206,
+ "CL": "",
+ "NE": "",
+ "AC": "PF14130"
+ }
+ ]
+ },
+ {
+ "title": "Borvo",
+ "contributors": [
+ "H\u00e9lo\u00efse Georjon"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1016/j.chom.2022.09.017"
+ },
+ {
+ "doi": "10.1016/j.cell.2023.02.029"
+ }
+ ],
+ "doi": "10.1016/j.chom.2022.09.017",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "CHAT",
+ "DE": "CHAT domain",
+ "GA": "24; 24;",
+ "TP": "Domain",
+ "ML": 289,
+ "CL": "CL0093",
+ "NE": "PDZ_2",
+ "AC": "PF12770"
+ }
+ ]
+ },
+ {
+ "title": "Retron",
+ "contributors": [
+ "Adi Millman",
+ "H\u00e9lo\u00efse Georjon",
+ "Aude Bernheim"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1016/j.cell.2020.09.065"
+ },
+ {
+ "doi": "10.1093/nar/gkaa1149"
+ },
+ {
+ "doi": "10.1038/s41586-022-05091-4"
+ },
+ {
+ "doi": "10.1126/science.aba0372"
+ },
+ {
+ "doi": "10.1038/s41564-022-01197-7"
+ },
+ {
+ "doi": "10.1093/nar/gkaa1149"
+ },
+ {
+ "doi": "10.1038/s41589-021-00927-y"
+ },
+ {
+ "doi": "10.1093/femsre/fuab025"
+ },
+ {
+ "doi": "10.1371/journal.pone.0285274"
+ },
+ {
+ "doi": "10.1038/s41596-023-00819-6"
+ },
+ {
+ "doi": "10.1093/nar/gkac177"
+ },
+ {
+ "doi": "10.1080/15476286.2019.1639310"
+ },
+ {
+ "doi": "10.1101/2023.08.16.553469"
+ }
+ ],
+ "doi": "10.1093/nar/gkaa1149",
+ "abstract": "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.\n",
+ "Sensor": "Monitor the integrity of the bacterial cell machinery",
+ "Activator": "Unknown",
+ "Effector": "Diverse",
+ "PFAM": [
+ {
+ "ID": "RVT_1",
+ "DE": "Reverse transcriptase (RNA-dependent DNA polymerase)",
+ "GA": "29.6; 29.6;",
+ "TP": "Domain",
+ "ML": 205,
+ "CL": "CL0027",
+ "NE": "",
+ "AC": "PF00078"
+ },
+ {
+ "ID": "Trypsin",
+ "DE": "Trypsin",
+ "GA": "20.6; 20.6;",
+ "TP": "Domain",
+ "ML": 220,
+ "CL": "CL0124",
+ "NE": "",
+ "AC": "PF00089"
+ },
+ {
+ "ID": "HTH_3",
+ "DE": "Helix-turn-helix",
+ "GA": "23; 23;",
+ "TP": "Domain",
+ "ML": 55,
+ "CL": "CL0123",
+ "NE": "",
+ "AC": "PF01381"
+ },
+ {
+ "ID": "TIR",
+ "DE": "TIR domain",
+ "GA": "21.3; 21.3;",
+ "TP": "Family",
+ "ML": 179,
+ "CL": "CL0173",
+ "NE": "",
+ "AC": "PF01582"
+ },
+ {
+ "ID": "DUF3800",
+ "DE": "Protein of unknown function (DUF3800)",
+ "GA": "21; 21;",
+ "TP": "Family",
+ "ML": 140,
+ "CL": "",
+ "NE": "",
+ "AC": "PF12686"
+ },
+ {
+ "ID": "HTH_19",
+ "DE": "Helix-turn-helix domain",
+ "GA": "30.2; 30.2;",
+ "TP": "Domain",
+ "ML": 64,
+ "CL": "CL0123",
+ "NE": "",
+ "AC": "PF12844"
+ },
+ {
+ "ID": "AAA_15",
+ "DE": "AAA ATPase domain",
+ "GA": "32.1; 32.1;",
+ "TP": "Domain",
+ "ML": 399,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13175"
+ },
+ {
+ "ID": "AAA_21",
+ "DE": "AAA domain, putative AbiEii toxin, Type IV TA system",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 304,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13304"
+ },
+ {
+ "ID": "Trypsin_2",
+ "DE": "Trypsin-like peptidase domain",
+ "GA": "27.6; 27.6;",
+ "TP": "Domain",
+ "ML": 144,
+ "CL": "CL0124",
+ "NE": "",
+ "AC": "PF13365"
+ },
+ {
+ "ID": "AAA_23",
+ "DE": "AAA domain",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 201,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13476"
+ },
+ {
+ "ID": "HTH_31",
+ "DE": "Helix-turn-helix domain",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 64,
+ "CL": "CL0123",
+ "NE": "",
+ "AC": "PF13560"
+ },
+ {
+ "ID": "TIR_2",
+ "DE": "TIR domain",
+ "GA": "28; 28;",
+ "TP": "Domain",
+ "ML": 122,
+ "CL": "CL0173",
+ "NE": "",
+ "AC": "PF13676"
+ }
+ ]
+ },
+ {
+ "title": "Avs",
+ "relevantAbstracts": [
+ {
+ "doi": "10.1126/science.aba0372"
+ },
+ {
+ "doi": "10.1126/science.abm4096"
+ }
+ ],
+ "contributors": [
+ "Alex Linyi Gao"
+ ],
+ "doi": "10.1126/science.aba0372",
+ "abstract": "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.\n",
+ "Sensor": "Sensing of phage protein",
+ "Activator": "Direct binding",
+ "Effector": "Diverse effectors (Nucleic acid degrading, putative Nucleotide modifying, putative Membrane disrupting)",
+ "PFAM": [
+ {
+ "ID": "Lactamase_B",
+ "DE": "Metallo-beta-lactamase superfamily",
+ "GA": "22.7; 21.9;",
+ "TP": "Domain",
+ "ML": 196,
+ "CL": "CL0381",
+ "NE": "",
+ "AC": "PF00753"
+ },
+ {
+ "ID": "SIR2_2",
+ "DE": "SIR2-like domain",
+ "GA": "24.5; 24.5;",
+ "TP": "Family",
+ "ML": 142,
+ "CL": "CL0063",
+ "NE": "",
+ "AC": "PF13289"
+ },
+ {
+ "ID": "Trypsin_2",
+ "DE": "Trypsin-like peptidase domain",
+ "GA": "27.6; 27.6;",
+ "TP": "Domain",
+ "ML": 144,
+ "CL": "CL0124",
+ "NE": "",
+ "AC": "PF13365"
+ }
+ ]
+ },
+ {
+ "title": "PD-T4-1",
+ "doi": "10.1038/s41564-022-01219-4",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "NOV_C",
+ "DE": "Protein NO VEIN, C-terminal",
+ "GA": "22.1; 22.1;",
+ "TP": "Family",
+ "ML": 91,
+ "CL": "CL0236",
+ "NE": "",
+ "AC": "PF13020"
+ }
+ ]
+ },
+ {
+ "title": "PD-T7-4",
+ "doi": "10.1038/s41564-022-01219-4",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "DUF4145",
+ "DE": "Domain of unknown function (DUF4145)",
+ "GA": "23.1; 23.1;",
+ "TP": "Domain",
+ "ML": 88,
+ "CL": "CL0291",
+ "NE": "",
+ "AC": "PF13643"
+ }
+ ]
+ },
+ {
+ "title": "pAgo",
+ "contributors": [
+ "Daan Swarts"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1016/j.cell.2022.03.012"
+ },
+ {
+ "doi": "10.1016/j.chom.2022.04.015"
+ },
+ {
+ "doi": "10.1038/s41564-022-01207-8"
+ },
+ {
+ "doi": "10.1038/s41586-020-2605-1"
+ },
+ {
+ "doi": "10.1186/1745-6150-4-29"
+ },
+ {
+ "doi": "10.1038/s41564-022-01239-0"
+ }
+ ],
+ "doi": "10.1186/1745-6150-4-29",
+ "abstract": "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. \nThe RNAi systems recognize the target RNA molecules via small guide RNAs that are completely or partially complementary to a region of the target. \nKey components of the RNAi systems are proteins of the Argonaute-PIWI family some of which function as slicers, \nthe nucleases that cleave the target RNA that is base-paired to a guide RNA. \nNumerous prokaryotes possess the CRISPR-associated system (CASS) of defense against phages and plasmids that is, in part, \nmechanistically analogous but not homologous to eukaryotic RNAi systems. \nMany prokaryotes also encode homologs of Argonaute-PIWI proteins but their functions remain unknown. \nRESULTS: We present a detailed analysis of Argonaute-PIWI protein sequences and the genomic neighborhoods of the respective genes in prokaryotes. \nWhereas 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.\n",
+ "Sensor": "Detecting invading nucleic acid",
+ "Activator": "Direct",
+ "Effector": "Diverse (Nucleotide modifyingn, Membrane disrupting)",
+ "PFAM": [
+ {
+ "ID": "Piwi",
+ "DE": "Piwi domain",
+ "GA": "28.9; 28.9;",
+ "TP": "Family",
+ "ML": 302,
+ "CL": "CL0219",
+ "NE": "",
+ "AC": "PF02171"
+ },
+ {
+ "ID": "SIR2_2",
+ "DE": "SIR2-like domain",
+ "GA": "24.5; 24.5;",
+ "TP": "Family",
+ "ML": 142,
+ "CL": "CL0063",
+ "NE": "",
+ "AC": "PF13289"
+ },
+ {
+ "ID": "TIR_2",
+ "DE": "TIR domain",
+ "GA": "28; 28;",
+ "TP": "Domain",
+ "ML": 122,
+ "CL": "CL0173",
+ "NE": "",
+ "AC": "PF13676"
+ },
+ {
+ "ID": "DUF4365",
+ "DE": "Domain of unknown function (DUF4365)",
+ "GA": "24.3; 24.3;",
+ "TP": "Domain",
+ "ML": 138,
+ "CL": "",
+ "NE": "",
+ "AC": "PF14280"
+ },
+ {
+ "ID": "DpnII-MboI",
+ "DE": "REase_DpnII-MboI",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 150,
+ "CL": "CL0236",
+ "NE": "",
+ "AC": "PF18742"
+ }
+ ]
+ },
+ {
+ "title": "Panchino_gp28",
+ "doi": "10.1038/nmicrobiol.2016.251",
+ "abstract": "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.\n",
+ "PFAM": [
+ {
+ "ID": "UPF0020",
+ "DE": "Putative RNA methylase family UPF0020",
+ "GA": "22.3; 22.3;",
+ "TP": "Domain",
+ "ML": 197,
+ "CL": "CL0063",
+ "NE": "",
+ "AC": "PF01170"
+ },
+ {
+ "ID": "N6_Mtase",
+ "DE": "N-6 DNA Methylase",
+ "GA": "20.4; 20.4;",
+ "TP": "Family",
+ "ML": 311,
+ "CL": "CL0063",
+ "NE": "",
+ "AC": "PF02384"
+ },
+ {
+ "ID": "HSDR_N_2",
+ "DE": "Type I restriction enzyme R protein N terminus (HSDR_N)",
+ "GA": "25; 25;",
+ "TP": "Domain",
+ "ML": 110,
+ "CL": "CL0236",
+ "NE": "",
+ "AC": "PF13588"
+ }
+ ]
+ },
+ {
+ "title": "AbiQ",
+ "doi": "10.1016/j.mib.2005.06.006",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "ToxN_toxin",
+ "DE": "Toxin ToxN, type III toxin-antitoxin system",
+ "GA": "25; 25;",
+ "TP": "Family",
+ "ML": 159,
+ "CL": "CL0010",
+ "NE": "",
+ "AC": "PF13958"
+ }
+ ]
+ },
+ {
+ "title": "Phrann_gp29_gp30",
+ "doi": "10.1038/nmicrobiol.2016.251",
+ "abstract": "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.\n",
+ "PFAM": [
+ {
+ "ID": "RelA_SpoT",
+ "DE": "Region found in RelA / SpoT proteins",
+ "GA": "27; 27;",
+ "TP": "Family",
+ "ML": 112,
+ "CL": "CL0260",
+ "NE": "",
+ "AC": "PF04607"
+ }
+ ]
+ },
+ {
+ "title": "DISARM",
+ "doi": "10.1038/s41564-017-0051-0",
+ "abstract": "The evolutionary pressure imposed by phage predation on bacteria and archaea has resulted in the development of effective anti-phage defence mechanisms, including restriction\u00e2\u20ac\u201cmodification and CRISPR\u00e2\u20ac\u201cCas\u00a0systems. Here, we report on a new defence system, DISARM (defence island system associated with restriction\u00e2\u20ac\u201cmodification), 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\u00a0D (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\u00e2\u20ac\u201cmodification systems. Our results suggest that DISARM is a new type of multi-gene restriction\u00e2\u20ac\u201cmodification module, expanding the arsenal of defence systems known to be at the disposal of prokaryotes against their viruses.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "DNA_methylase",
+ "DE": "C-5 cytosine-specific DNA methylase",
+ "GA": "22; 22;",
+ "TP": "Domain",
+ "ML": 324,
+ "CL": "CL0063",
+ "NE": "",
+ "AC": "PF00145"
+ },
+ {
+ "ID": "SNF2-rel_dom",
+ "DE": "SNF2-related domain",
+ "GA": "23.9; 23.9;",
+ "TP": "Domain",
+ "ML": 290,
+ "CL": "CL0023",
+ "NE": "Bromodomain",
+ "AC": "PF00176"
+ },
+ {
+ "ID": "Helicase_C",
+ "DE": "Helicase conserved C-terminal domain",
+ "GA": "23.5; 23.5;",
+ "TP": "Domain",
+ "ML": 110,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF00271"
+ },
+ {
+ "ID": "ResIII",
+ "DE": "Type III restriction enzyme, res subunit",
+ "GA": "22.5; 22.5;",
+ "TP": "Family",
+ "ML": 164,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF04851"
+ },
+ {
+ "ID": "MZB",
+ "DE": "MrfA Zn-binding domain",
+ "GA": "24.2; 24.2;",
+ "TP": "Domain",
+ "ML": 80,
+ "CL": "",
+ "NE": "",
+ "AC": "PF09369"
+ },
+ {
+ "ID": "PLDc_2",
+ "DE": "PLD-like domain",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 132,
+ "CL": "CL0479",
+ "NE": "",
+ "AC": "PF13091"
+ }
+ ]
+ },
+ {
+ "title": "Tiamat",
+ "contributors": [
+ "Helena Shomar, Marie Guillaume"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1016/j.chom.2022.09.017"
+ }
+ ],
+ "doi": "10.1016/j.chom.2022.09.017",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "Peptidase_C14",
+ "DE": "Caspase domain",
+ "GA": "21.4; 21.4;",
+ "TP": "Domain",
+ "ML": 234,
+ "CL": "CL0093",
+ "NE": "",
+ "AC": "PF00656"
+ },
+ {
+ "ID": "NOV_C",
+ "DE": "Protein NO VEIN, C-terminal",
+ "GA": "22.1; 22.1;",
+ "TP": "Family",
+ "ML": 91,
+ "CL": "CL0236",
+ "NE": "",
+ "AC": "PF13020"
+ }
+ ]
+ },
+ {
+ "title": "AbiO",
+ "doi": "10.1016/j.mib.2005.06.006",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "Viral_helicase1",
+ "DE": "Viral (Superfamily 1) RNA helicase",
+ "GA": "21; 21;",
+ "TP": "Family",
+ "ML": 228,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF01443"
+ },
+ {
+ "ID": "SLFN-g3_helicase",
+ "DE": "Schlafen group 3, DNA/RNA helicase domain",
+ "GA": "20.3; 20.3;",
+ "TP": "Domain",
+ "ML": 355,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF09848"
+ }
+ ]
+ },
+ {
+ "title": "AbiC",
+ "doi": "10.1016/j.mib.2005.06.006",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "putAbiC",
+ "DE": "Putative phage abortive infection protein",
+ "GA": "22; 22;",
+ "TP": "Family",
+ "ML": 80,
+ "CL": "",
+ "NE": "",
+ "AC": "PF16872"
+ }
+ ]
+ },
+ {
+ "title": "Rst_HelicaseDUF2290",
+ "contributors": [
+ "Ernest Mordret"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1016/j.chom.2022.02.018"
+ }
+ ],
+ "doi": "10.1016/j.chom.2022.02.018",
+ "abstract": "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.\u00a0coli 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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "DUF2290",
+ "DE": "Uncharacterized conserved protein (DUF2290)",
+ "GA": "25; 25;",
+ "TP": "Family",
+ "ML": 195,
+ "CL": "",
+ "NE": "",
+ "AC": "PF10053"
+ },
+ {
+ "ID": "UvrD_C_2",
+ "DE": "UvrD-like helicase C-terminal domain",
+ "GA": "27.4; 27.4;",
+ "TP": "Domain",
+ "ML": 52,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13538"
+ }
+ ]
+ },
+ {
+ "title": "AbiP2",
+ "doi": "10.1016/j.mib.2005.06.006",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "RVT_1",
+ "DE": "Reverse transcriptase (RNA-dependent DNA polymerase)",
+ "GA": "29.6; 29.6;",
+ "TP": "Domain",
+ "ML": 205,
+ "CL": "CL0027",
+ "NE": "",
+ "AC": "PF00078"
+ }
+ ]
+ },
+ {
+ "title": "Rst_2TM_1TM_TIR",
+ "contributors": [
+ "Alba Herrero del Valle"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1016/j.chom.2022.02.018"
+ }
+ ],
+ "doi": "10.1016/j.chom.2022.02.018",
+ "abstract": "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.\u00a0coli 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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "TIR_2",
+ "DE": "TIR domain",
+ "GA": "28; 28;",
+ "TP": "Domain",
+ "ML": 122,
+ "CL": "CL0173",
+ "NE": "",
+ "AC": "PF13676"
+ }
+ ]
+ },
+ {
+ "title": "Viperin",
+ "contributors": [
+ "Marian Dominguez-Mirazo"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1038/s41586-020-2762-2"
+ }
+ ],
+ "doi": "10.1038/s41586-020-2762-2",
+ "abstract": "Viperin is an interferon-induced cellular protein that is conserved in animals. It has\u00a0previously 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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Direct binding",
+ "Effector": "Nucleotide modifying",
+ "PFAM": [
+ {
+ "ID": "Radical_SAM",
+ "DE": "Radical SAM superfamily",
+ "GA": "29.5; 29.5;",
+ "TP": "Domain",
+ "ML": 167,
+ "CL": "CL0036",
+ "NE": "Fer4",
+ "AC": "PF04055"
+ },
+ {
+ "ID": "Fer4_12",
+ "DE": "4Fe-4S single cluster domain",
+ "GA": "22; 22;",
+ "TP": "Domain",
+ "ML": 137,
+ "CL": "CL0344",
+ "NE": "",
+ "AC": "PF13353"
+ }
+ ]
+ },
+ {
+ "title": "MADS",
+ "doi": "10.1101/2023.03.30.534895",
+ "abstract": "The constant arms race between bacteria and their phages has resulted in a large diversity of bacterial defence systems1,2, with many bacteria carrying several systems3,4. In response, phages often carry counter-defence genes5-9. If and how bacterial defence mechanisms interact to protect against phages with counter-defence genes remains unclear. Here, we report the existence of a novel defence system, coined MADS (Methylation Associated Defence System), which is located in a strongly conserved genomic defence hotspot in Pseudomonas aeruginosa and distributed across Gram-positive and Gram-negative bacteria. We find that the natural co-existence of MADS and a Type IE CRISPR-Cas adaptive immune system in the genome of P. aeruginosa SMC4386 provides synergistic levels of protection against phage DMS3, which carries an anti-CRISPR (acr) gene. Previous work has demonstrated that Acr-phages need to cooperate to overcome CRISPR immunity, with a first sacrificial phage causing host immunosuppression to enable successful secondary phage infections10,11. Modelling and experiments show that the co-existence of MADS and CRISPR-Cas provides strong and durable protection against Acr-phages by disrupting their cooperation and limiting the spread of mutants that overcome MADS. These data reveal that combining bacterial defences can robustly neutralise phage with counter-defence genes, even if each defence on its own can be readily by-passed, which is key to understanding how selection acts on defence combinations and their coevolutionary consequences.\n",
+ "PFAM": [
+ {
+ "ID": "Pkinase",
+ "DE": "Protein kinase domain",
+ "GA": "31.7; 31.7;",
+ "TP": "Domain",
+ "ML": 263,
+ "CL": "CL0016",
+ "NE": "",
+ "AC": "PF00069"
+ },
+ {
+ "ID": "UPF0020",
+ "DE": "Putative RNA methylase family UPF0020",
+ "GA": "22.3; 22.3;",
+ "TP": "Domain",
+ "ML": 197,
+ "CL": "CL0063",
+ "NE": "",
+ "AC": "PF01170"
+ },
+ {
+ "ID": "N6_Mtase",
+ "DE": "N-6 DNA Methylase",
+ "GA": "20.4; 20.4;",
+ "TP": "Family",
+ "ML": 311,
+ "CL": "CL0063",
+ "NE": "",
+ "AC": "PF02384"
+ },
+ {
+ "ID": "PK_Tyr_Ser-Thr",
+ "DE": "Protein tyrosine and serine/threonine kinase",
+ "GA": "23.1; 23.1;",
+ "TP": "Domain",
+ "ML": 258,
+ "CL": "CL0016",
+ "NE": "",
+ "AC": "PF07714"
+ },
+ {
+ "ID": "NERD",
+ "DE": "Nuclease-related domain",
+ "GA": "22.1; 22.1;",
+ "TP": "Family",
+ "ML": 111,
+ "CL": "CL0236",
+ "NE": "",
+ "AC": "PF08378"
+ },
+ {
+ "ID": "HTH_17",
+ "DE": "Helix-turn-helix domain",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 51,
+ "CL": "CL0123",
+ "NE": "",
+ "AC": "PF12728"
+ },
+ {
+ "ID": "AAA_21",
+ "DE": "AAA domain, putative AbiEii toxin, Type IV TA system",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 304,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13304"
+ },
+ {
+ "ID": "HSDR_N_2",
+ "DE": "Type I restriction enzyme R protein N terminus (HSDR_N)",
+ "GA": "25; 25;",
+ "TP": "Domain",
+ "ML": 110,
+ "CL": "CL0236",
+ "NE": "",
+ "AC": "PF13588"
+ }
+ ]
+ },
+ {
+ "title": "Rst_3HP",
+ "contributors": [
+ "Alba Herrero del Valle"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1016/j.chom.2022.02.018"
+ }
+ ],
+ "doi": "10.1016/j.chom.2022.02.018",
+ "abstract": "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.\u00a0coli 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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": []
+ },
+ {
+ "title": "Gao_Her",
+ "doi": "10.1126/science.aba0372",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "DUF87",
+ "DE": "Helicase HerA, central domain",
+ "GA": "23.2; 23.2;",
+ "TP": "Domain",
+ "ML": 220,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF01935"
+ },
+ {
+ "ID": "TrwB_AAD_bind",
+ "DE": "Type IV secretion-system coupling protein DNA-binding domain",
+ "GA": "20.5; 20.5;",
+ "TP": "Domain",
+ "ML": 387,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF10412"
+ },
+ {
+ "ID": "SIR2_2",
+ "DE": "SIR2-like domain",
+ "GA": "24.5; 24.5;",
+ "TP": "Family",
+ "ML": 142,
+ "CL": "CL0063",
+ "NE": "",
+ "AC": "PF13289"
+ }
+ ]
+ },
+ {
+ "title": "PD-T7-2",
+ "doi": "10.1038/s41564-022-01219-4",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "DUF87",
+ "DE": "Helicase HerA, central domain",
+ "GA": "23.2; 23.2;",
+ "TP": "Domain",
+ "ML": 220,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF01935"
+ },
+ {
+ "ID": "SIR2_2",
+ "DE": "SIR2-like domain",
+ "GA": "24.5; 24.5;",
+ "TP": "Family",
+ "ML": 142,
+ "CL": "CL0063",
+ "NE": "",
+ "AC": "PF13289"
+ }
+ ]
+ },
+ {
+ "title": "PrrC",
+ "contributors": [
+ "Ernest Mordret"
+ ],
+ "relevant abstracts": [
+ {
+ "doi": "10.1186/1743-422X-7-360"
+ },
+ {
+ "doi": "10.1006/jmbi.1995.0343"
+ }
+ ],
+ "doi": "10.1186/1743-422X-7-360",
+ "abstract": "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.\n",
+ "Sensor": "Monitor the integrity of the bacterial cell machinery",
+ "Activator": "Direct",
+ "Effector": "Nucleic acid degrading",
+ "PFAM": [
+ {
+ "ID": "DEAD",
+ "DE": "DEAD/DEAH box helicase",
+ "GA": "26; 24.1;",
+ "TP": "Domain",
+ "ML": 166,
+ "CL": "CL0023",
+ "NE": "SPRY",
+ "AC": "PF00270"
+ },
+ {
+ "ID": "N6_Mtase",
+ "DE": "N-6 DNA Methylase",
+ "GA": "20.4; 20.4;",
+ "TP": "Family",
+ "ML": 311,
+ "CL": "CL0063",
+ "NE": "",
+ "AC": "PF02384"
+ },
+ {
+ "ID": "HSDR_N",
+ "DE": "Type I restriction enzyme R protein N terminus (HSDR_N)",
+ "GA": "25.1; 25.1;",
+ "TP": "Family",
+ "ML": 195,
+ "CL": "CL0236",
+ "NE": "",
+ "AC": "PF04313"
+ },
+ {
+ "ID": "ResIII",
+ "DE": "Type III restriction enzyme, res subunit",
+ "GA": "22.5; 22.5;",
+ "TP": "Family",
+ "ML": 164,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF04851"
+ },
+ {
+ "ID": "EcoR124_C",
+ "DE": "Type I restriction and modification enzyme - subunit R C terminal",
+ "GA": "23.1; 23.1;",
+ "TP": "Domain",
+ "ML": 260,
+ "CL": "",
+ "NE": "",
+ "AC": "PF12008"
+ },
+ {
+ "ID": "HsdM_N",
+ "DE": "HsdM N-terminal domain",
+ "GA": "24.5; 24.5;",
+ "TP": "Domain",
+ "ML": 138,
+ "CL": "",
+ "NE": "",
+ "AC": "PF12161"
+ },
+ {
+ "ID": "AAA_13",
+ "DE": "AAA domain",
+ "GA": "36; 36;",
+ "TP": "Domain",
+ "ML": 714,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13166"
+ },
+ {
+ "ID": "SWI2_SNF2",
+ "DE": "SWI2/SNF2 ATPase",
+ "GA": "26.7; 26.7;",
+ "TP": "Family",
+ "ML": 222,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF18766"
+ }
+ ]
+ },
+ {
+ "title": "SoFIC",
+ "doi": "10.1016/j.chom.2022.09.017",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "Fic",
+ "DE": "Fic/DOC family",
+ "GA": "24; 24;",
+ "TP": "Family",
+ "ML": 93,
+ "CL": "",
+ "NE": "",
+ "AC": "PF02661"
+ },
+ {
+ "ID": "Fic_N",
+ "DE": "Fic/DOC family N-terminal",
+ "GA": "26.7; 26.7;",
+ "TP": "Family",
+ "ML": 82,
+ "CL": "",
+ "NE": "",
+ "AC": "PF13784"
+ }
+ ]
+ },
+ {
+ "title": "Azaca",
+ "doi": "10.1016/j.chom.2022.09.017",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "Helicase_C",
+ "DE": "Helicase conserved C-terminal domain",
+ "GA": "23.5; 23.5;",
+ "TP": "Domain",
+ "ML": 110,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF00271"
+ }
+ ]
+ },
+ {
+ "title": "Rst_Hydrolase-3Tm",
+ "doi": "10.1016/j.chom.2022.02.018",
+ "abstract": "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.\u00a0coli 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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "Hydrolase_like",
+ "DE": "HAD-hyrolase-like",
+ "GA": "22; 22;",
+ "TP": "Domain",
+ "ML": 75,
+ "CL": "CL0137",
+ "NE": "",
+ "AC": "PF13242"
+ },
+ {
+ "ID": "HAD_2",
+ "DE": "Haloacid dehalogenase-like hydrolase",
+ "GA": "23.8; 23.8;",
+ "TP": "Family",
+ "ML": 178,
+ "CL": "CL0137",
+ "NE": "",
+ "AC": "PF13419"
+ }
+ ]
+ },
+ {
+ "title": "GAPS2",
+ "doi": "10.1101/2023.03.28.534373",
+ "abstract": "Bacteria are found in ongoing conflicts with rivals and predators, which lead to an evolutionary arms race and the development of innate and adaptive immune systems. Although diverse bacterial immunity mechanisms have been recently identified, many remain unknown, and their dissemination within bacterial populations is poorly understood. Here, we describe a widespread genetic element, defined by the Gamma-Mobile-Trio (GMT) proteins, that serves as a mobile bacterial weapons armory. We show that GMT islands have cargo comprising various combinations of secreted antibacterial toxins, anti-phage defense systems, and secreted anti-eukaryotic toxins. This finding led us to identify four new anti-phage defense systems encoded within GMT islands and reveal their active domains and mechanisms of action. We also find the phage protein that triggers the activation of one of these systems. Thus, we can identify novel toxins and defense systems by investigating proteins of unknown function encoded within GMT islands. Our findings imply that the concept of \"defense islands\" may be broadened to include other types of bacterial innate immunity mechanisms, such as antibacterial and anti-eukaryotic toxins that appear to stockpile with anti-phage defense systems within GMT weapon islands.\n",
+ "PFAM": [
+ {
+ "ID": "BRCT",
+ "DE": "BRCA1 C Terminus (BRCT) domain",
+ "GA": "21.3; 21.3;",
+ "TP": "Family",
+ "ML": 78,
+ "CL": "CL0459",
+ "NE": "",
+ "AC": "PF00533"
+ },
+ {
+ "ID": "DNA_ligase_aden",
+ "DE": "NAD-dependent DNA ligase adenylation domain",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 319,
+ "CL": "CL0179",
+ "NE": "",
+ "AC": "PF01653"
+ },
+ {
+ "ID": "DNA_ligase_ZBD",
+ "DE": "NAD-dependent DNA ligase C4 zinc finger domain",
+ "GA": "25.8; 25.8;",
+ "TP": "Domain",
+ "ML": 27,
+ "CL": "",
+ "NE": "",
+ "AC": "PF03119"
+ },
+ {
+ "ID": "DNA_ligase_OB",
+ "DE": "NAD-dependent DNA ligase OB-fold domain",
+ "GA": "32.9; 32.9;",
+ "TP": "Domain",
+ "ML": 79,
+ "CL": "CL0021",
+ "NE": "",
+ "AC": "PF03120"
+ },
+ {
+ "ID": "HHH_2",
+ "DE": "Helix-hairpin-helix motif",
+ "GA": "27; 27;",
+ "TP": "Motif",
+ "ML": 64,
+ "CL": "CL0198",
+ "NE": "",
+ "AC": "PF12826"
+ },
+ {
+ "ID": "HHH_5",
+ "DE": "Helix-hairpin-helix domain",
+ "GA": "27; 17;",
+ "TP": "Domain",
+ "ML": 57,
+ "CL": "CL0198",
+ "NE": "",
+ "AC": "PF14520"
+ }
+ ]
+ },
+ {
+ "title": "Shango",
+ "contributors": [
+ "Hugo Vaysset",
+ "Aude Bernheim"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1016/j.chom.2022.09.017"
+ },
+ {
+ "doi": "10.1093/nar/gkad317"
+ }
+ ],
+ "doi": "10.1016/j.chom.2022.09.017",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "DEAD",
+ "DE": "DEAD/DEAH box helicase",
+ "GA": "26; 24.1;",
+ "TP": "Domain",
+ "ML": 166,
+ "CL": "CL0023",
+ "NE": "SPRY",
+ "AC": "PF00270"
+ },
+ {
+ "ID": "Helicase_C",
+ "DE": "Helicase conserved C-terminal domain",
+ "GA": "23.5; 23.5;",
+ "TP": "Domain",
+ "ML": 110,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF00271"
+ },
+ {
+ "ID": "TerB",
+ "DE": "Tellurite resistance protein TerB",
+ "GA": "24.4; 24.4;",
+ "TP": "Family",
+ "ML": 118,
+ "CL": "CL0414",
+ "NE": "",
+ "AC": "PF05099"
+ },
+ {
+ "ID": "BrxC_BrxD",
+ "DE": "BREX system ATP-binding protein BrxC/D",
+ "GA": "22.2; 22.2;",
+ "TP": "Domain",
+ "ML": 414,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF10923"
+ },
+ {
+ "ID": "TerB_N",
+ "DE": "TerB N-terminal domain",
+ "GA": "25; 25;",
+ "TP": "Family",
+ "ML": 208,
+ "CL": "",
+ "NE": "",
+ "AC": "PF13208"
+ },
+ {
+ "ID": "TerB_C",
+ "DE": "TerB-C domain",
+ "GA": "26.3; 26.3;",
+ "TP": "Domain",
+ "ML": 145,
+ "CL": "",
+ "NE": "",
+ "AC": "PF15615"
+ }
+ ]
+ },
+ {
+ "title": "PD-Lambda-3",
+ "contributors": [
+ "H\u00e9lo\u00efse Georjon"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1038/s41564-022-01219-4"
+ }
+ ],
+ "doi": "10.1038/s41564-022-01219-4",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "Hypoth_Ymh",
+ "DE": "Protein of unknown function (Hypoth_ymh)",
+ "GA": "25; 25;",
+ "TP": "Family",
+ "ML": 119,
+ "CL": "",
+ "NE": "",
+ "AC": "PF09509"
+ }
+ ]
+ },
+ {
+ "title": "ShosTA",
+ "relevantAbstracts": [
+ {
+ "doi": "10.1016/j.chom.2022.09.017"
+ },
+ {
+ "doi": "10.1016/j.chom.2022.02.018"
+ },
+ {
+ "doi": "10.1101/gr.133850.111"
+ }
+ ],
+ "doi": "10.1016/j.chom.2022.09.017",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "DNA_processg_A",
+ "DE": "DNA recombination-mediator protein A",
+ "GA": "29.6; 29.6;",
+ "TP": "Family",
+ "ML": 211,
+ "CL": "CL0349",
+ "NE": "",
+ "AC": "PF02481"
+ }
+ ]
+ },
+ {
+ "title": "Abi2",
+ "relevantAbstracts": [
+ {
+ "doi": "10.1016/j.mib.2005.06.006"
+ }
+ ],
+ "doi": "10.1016/j.mib.2005.06.006",
+ "abstract": "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.\n",
+ "Sensor": "",
+ "Activator": "",
+ "Effector": "",
+ "PFAM": [
+ {
+ "ID": "Abi_2",
+ "DE": "Abi-like protein",
+ "GA": "25.6; 25.6;",
+ "TP": "Family",
+ "ML": 181,
+ "CL": "",
+ "NE": "",
+ "AC": "PF07751"
+ }
+ ]
+ },
+ {
+ "title": "AbiT",
+ "doi": "10.1016/j.mib.2005.06.006",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "AbiTii",
+ "DE": "AbiTii",
+ "GA": "27.6; 27.6;",
+ "TP": "Domain",
+ "ML": 186,
+ "CL": "",
+ "NE": "",
+ "AC": "PF18864"
+ }
+ ]
+ },
+ {
+ "title": "Septu",
+ "doi": "10.1126/science.aar4120",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "AAA_15",
+ "DE": "AAA ATPase domain",
+ "GA": "32.1; 32.1;",
+ "TP": "Domain",
+ "ML": 399,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13175"
+ },
+ {
+ "ID": "AAA_21",
+ "DE": "AAA domain, putative AbiEii toxin, Type IV TA system",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 304,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13304"
+ },
+ {
+ "ID": "AAA_23",
+ "DE": "AAA domain",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 201,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13476"
+ }
+ ]
+ },
+ {
+ "title": "PD-Lambda-1",
+ "contributors": [
+ "Alba Herrero del Valle"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1038/s41564-022-01219-4"
+ }
+ ],
+ "doi": "10.1038/s41564-022-01219-4",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "T5orf172",
+ "DE": "T5orf172 domain",
+ "GA": "20; 20;",
+ "TP": "Domain",
+ "ML": 101,
+ "CL": "CL0418",
+ "NE": "",
+ "AC": "PF10544"
+ },
+ {
+ "ID": "DUF4041",
+ "DE": "Domain of unknown function (DUF4041)",
+ "GA": "27; 27;",
+ "TP": "Family",
+ "ML": 56,
+ "CL": "",
+ "NE": "",
+ "AC": "PF13250"
+ },
+ {
+ "ID": "MUG113",
+ "DE": "Meiotically up-regulated gene 113",
+ "GA": "22.3; 22;",
+ "TP": "Family",
+ "ML": 73,
+ "CL": "CL0418",
+ "NE": "",
+ "AC": "PF13455"
+ }
+ ]
+ },
+ {
+ "title": "Hachiman",
+ "doi": "10.1126/science.aar4120",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "DEAD",
+ "DE": "DEAD/DEAH box helicase",
+ "GA": "26; 24.1;",
+ "TP": "Domain",
+ "ML": 166,
+ "CL": "CL0023",
+ "NE": "SPRY",
+ "AC": "PF00270"
+ },
+ {
+ "ID": "Helicase_C",
+ "DE": "Helicase conserved C-terminal domain",
+ "GA": "23.5; 23.5;",
+ "TP": "Domain",
+ "ML": 110,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF00271"
+ },
+ {
+ "ID": "ResIII",
+ "DE": "Type III restriction enzyme, res subunit",
+ "GA": "22.5; 22.5;",
+ "TP": "Family",
+ "ML": 164,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF04851"
+ },
+ {
+ "ID": "HamA",
+ "DE": "HamA",
+ "GA": "25; 25;",
+ "TP": "Family",
+ "ML": 230,
+ "CL": "",
+ "NE": "",
+ "AC": "PF08878"
+ },
+ {
+ "ID": "Cap4_nuclease",
+ "DE": "Cap4, dsDNA endonuclease domain",
+ "GA": "26.2; 26.2;",
+ "TP": "Family",
+ "ML": 206,
+ "CL": "",
+ "NE": "",
+ "AC": "PF14130"
+ }
+ ]
+ },
+ {
+ "title": "PD-T4-8",
+ "contributors": [
+ "Alba Herrero del Valle"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1371/journal.pgen.1010065"
+ }
+ ],
+ "doi": "10.1038/s41564-022-01219-4",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "SduA_C",
+ "DE": "Shedu protein SduA, C-terminal",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 160,
+ "CL": "CL0236",
+ "NE": "",
+ "AC": "PF14082"
+ }
+ ]
+ },
+ {
+ "title": "RM",
+ "doi": "10.1093/nar/gku734",
+ "abstract": "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.\n",
+ "Sensor": "Detecting invading nucleic acid",
+ "Activator": "Direct",
+ "Effector": "Nucleic acid degrading",
+ "PFAM": [
+ {
+ "ID": "DEAD",
+ "DE": "DEAD/DEAH box helicase",
+ "GA": "26; 24.1;",
+ "TP": "Domain",
+ "ML": 166,
+ "CL": "CL0023",
+ "NE": "SPRY",
+ "AC": "PF00270"
+ },
+ {
+ "ID": "N6_Mtase",
+ "DE": "N-6 DNA Methylase",
+ "GA": "20.4; 20.4;",
+ "TP": "Family",
+ "ML": 311,
+ "CL": "CL0063",
+ "NE": "",
+ "AC": "PF02384"
+ },
+ {
+ "ID": "HSDR_N",
+ "DE": "Type I restriction enzyme R protein N terminus (HSDR_N)",
+ "GA": "25.1; 25.1;",
+ "TP": "Family",
+ "ML": 195,
+ "CL": "CL0236",
+ "NE": "",
+ "AC": "PF04313"
+ },
+ {
+ "ID": "ResIII",
+ "DE": "Type III restriction enzyme, res subunit",
+ "GA": "22.5; 22.5;",
+ "TP": "Family",
+ "ML": 164,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF04851"
+ },
+ {
+ "ID": "EcoR124_C",
+ "DE": "Type I restriction and modification enzyme - subunit R C terminal",
+ "GA": "23.1; 23.1;",
+ "TP": "Domain",
+ "ML": 260,
+ "CL": "",
+ "NE": "",
+ "AC": "PF12008"
+ },
+ {
+ "ID": "HsdM_N",
+ "DE": "HsdM N-terminal domain",
+ "GA": "24.5; 24.5;",
+ "TP": "Domain",
+ "ML": 138,
+ "CL": "",
+ "NE": "",
+ "AC": "PF12161"
+ },
+ {
+ "ID": "SWI2_SNF2",
+ "DE": "SWI2/SNF2 ATPase",
+ "GA": "26.7; 26.7;",
+ "TP": "Family",
+ "ML": 222,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF18766"
+ }
+ ]
+ },
+ {
+ "title": "AbiH",
+ "relevantAbstracts": [
+ {
+ "doi": "10.1023/A:1002027321171"
+ },
+ {
+ "doi": "10.1016/j.mib.2005.06.006"
+ },
+ {
+ "doi": "10.1111/j.1574-6968.1996.tb08446.x"
+ }
+ ],
+ "doi": "10.1111/j.1574-6968.1996.tb08446.x",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "AbiH",
+ "DE": "Bacteriophage abortive infection AbiH",
+ "GA": "30.9; 30.9;",
+ "TP": "Family",
+ "ML": 261,
+ "CL": "",
+ "NE": "",
+ "AC": "PF14253"
+ }
+ ]
+ },
+ {
+ "title": "Gabija",
+ "contributors": [
+ "Nathalie Bechon"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1093/nar/gkab277"
+ },
+ {
+ "doi": "10.1126/science.aar4120"
+ },
+ {
+ "doi": "10.1016/j.chom.2023.06.014"
+ },
+ {
+ "doi": "10.1038/s41586-023-06855-2"
+ },
+ {
+ "doi": "10.1038/s41586-023-06869-w"
+ }
+ ],
+ "doi": "10.1126/science.aar4120",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Direct",
+ "Effector": "Degrading nucleic acids",
+ "PFAM": [
+ {
+ "ID": "UvrD-helicase",
+ "DE": "UvrD/REP helicase N-terminal domain",
+ "GA": "23; 23;",
+ "TP": "Domain",
+ "ML": 271,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF00580"
+ },
+ {
+ "ID": "DUF2813",
+ "DE": "Protein of unknown function (DUF2813)",
+ "GA": "21; 21;",
+ "TP": "Family",
+ "ML": 372,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF11398"
+ },
+ {
+ "ID": "AAA_15",
+ "DE": "AAA ATPase domain",
+ "GA": "32.1; 32.1;",
+ "TP": "Domain",
+ "ML": 399,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13175"
+ },
+ {
+ "ID": "AAA_19",
+ "DE": "AAA domain",
+ "GA": "25.1; 25.1;",
+ "TP": "Domain",
+ "ML": 135,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13245"
+ },
+ {
+ "ID": "AAA_21",
+ "DE": "AAA domain, putative AbiEii toxin, Type IV TA system",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 304,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13304"
+ },
+ {
+ "ID": "UvrD_C",
+ "DE": "UvrD-like helicase C-terminal domain",
+ "GA": "25.6; 25.6;",
+ "TP": "Domain",
+ "ML": 350,
+ "CL": "CL0023",
+ "NE": "RNase_T",
+ "AC": "PF13361"
+ },
+ {
+ "ID": "AAA_23",
+ "DE": "AAA domain",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 201,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13476"
+ }
+ ]
+ },
+ {
+ "title": "Detocs",
+ "contributors": [
+ "Fran\u00e7ois Rousset",
+ "Nathalie Bechon"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1016/j.cell.2023.07.020"
+ }
+ ],
+ "doi": "10.1016/j.cell.2023.07.020",
+ "abstract": "During viral infection, cells can deploy immune strategies that deprive viruses of molecules essential for their replication. Here, we report a family of immune effectors in bacteria that, upon phage infection, degrade cellular adenosine triphosphate (ATP) and deoxyadenosine triphosphate (dATP) by cleaving the N-glycosidic bond between the adenine and sugar moieties. These ATP nucleosidase effectors are widely distributed within multiple bacterial defense systems, including cyclic oligonucleotide-based antiviral signaling systems (CBASS), prokaryotic argonautes, and nucleotide-binding leucine-rich repeat (NLR)-like proteins, and we show that ATP and dATP degradation during infection halts phage propagation. By analyzing homologs of the immune ATP nucleosidase domain, we discover and characterize Detocs, a family of bacterial defense systems with a two-component phosphotransfer-signaling architecture. The immune ATP nucleosidase domain is also encoded within diverse eukaryotic proteins with immune-like architectures, and we show biochemically that eukaryotic homologs preserve the ATP nucleosidase activity. Our findings suggest that ATP and dATP degradation is a cell-autonomous innate immune strategy conserved across the tree of life.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Nucleotide modifying",
+ "PFAM": [
+ {
+ "ID": "PNP_UDP_1",
+ "DE": "Phosphorylase superfamily",
+ "GA": "25.1; 25.1;",
+ "TP": "Domain",
+ "ML": 233,
+ "CL": "CL0408",
+ "NE": "",
+ "AC": "PF01048"
+ },
+ {
+ "ID": "DpnII-MboI",
+ "DE": "REase_DpnII-MboI",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 150,
+ "CL": "CL0236",
+ "NE": "",
+ "AC": "PF18742"
+ }
+ ]
+ },
+ {
+ "title": "Druantia",
+ "doi": "10.1126/science.aar4120",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "DNA_methylase",
+ "DE": "C-5 cytosine-specific DNA methylase",
+ "GA": "22; 22;",
+ "TP": "Domain",
+ "ML": 324,
+ "CL": "CL0063",
+ "NE": "",
+ "AC": "PF00145"
+ },
+ {
+ "ID": "DEAD",
+ "DE": "DEAD/DEAH box helicase",
+ "GA": "26; 24.1;",
+ "TP": "Domain",
+ "ML": 166,
+ "CL": "CL0023",
+ "NE": "SPRY",
+ "AC": "PF00270"
+ },
+ {
+ "ID": "Helicase_C",
+ "DE": "Helicase conserved C-terminal domain",
+ "GA": "23.5; 23.5;",
+ "TP": "Domain",
+ "ML": 110,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF00271"
+ },
+ {
+ "ID": "ResIII",
+ "DE": "Type III restriction enzyme, res subunit",
+ "GA": "22.5; 22.5;",
+ "TP": "Family",
+ "ML": 164,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF04851"
+ },
+ {
+ "ID": "MZB",
+ "DE": "MrfA Zn-binding domain",
+ "GA": "24.2; 24.2;",
+ "TP": "Domain",
+ "ML": 80,
+ "CL": "",
+ "NE": "",
+ "AC": "PF09369"
+ },
+ {
+ "ID": "DruA",
+ "DE": "Druantia protein DruA",
+ "GA": "27; 27;",
+ "TP": "Family",
+ "ML": 297,
+ "CL": "",
+ "NE": "",
+ "AC": "PF14236"
+ }
+ ]
+ },
+ {
+ "title": "AbiV",
+ "doi": "10.1128/AEM.00780-08",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "HEPN_AbiV",
+ "DE": "AbiV",
+ "GA": "27.1; 27.1;",
+ "TP": "Domain",
+ "ML": 157,
+ "CL": "CL0291",
+ "NE": "",
+ "AC": "PF18728"
+ }
+ ]
+ },
+ {
+ "title": "Olokun",
+ "contributors": [
+ "Helena Shomar",
+ "Marie Guillaume"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1016/j.chom.2022.09.017"
+ }
+ ],
+ "doi": "10.1016/j.chom.2022.09.017",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "Adaptin_N",
+ "DE": "Adaptin N terminal region",
+ "GA": "37; 37;",
+ "TP": "Repeat",
+ "ML": 524,
+ "CL": "CL0020",
+ "NE": "",
+ "AC": "PF01602"
+ },
+ {
+ "ID": "DpnII-MboI",
+ "DE": "REase_DpnII-MboI",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 150,
+ "CL": "CL0236",
+ "NE": "",
+ "AC": "PF18742"
+ }
+ ]
+ },
+ {
+ "title": "dCTPdeaminase",
+ "contributors": [
+ "Nathalie Bechon"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1038/s41564-022-01162-4"
+ },
+ {
+ "doi": "10.1038/s41564-022-01158-0"
+ }
+ ],
+ "doi": "10.1038/s41564-022-01158-0",
+ "abstract": "DNA viruses and retroviruses consume large quantities of deoxynucleotides (dNTPs) when replicating. The human antiviral factor SAMHD1 takes advantage of this vulnerability in the viral lifecycle, and inhibits viral replication by degrading dNTPs into their constituent deoxynucleosides and inorganic phosphate. Here, we report that bacteria use a similar strategy to defend against bacteriophage infection. We identify a family of defensive bacterial deoxycytidine triphosphate (dCTP) deaminase proteins that convert dCTP into deoxyuracil nucleotides in response to phage infection. We also identify a family of phage resistance genes that encode deoxyguanosine triphosphatase (dGTPase) enzymes, which degrade dGTP into phosphate-free deoxyguanosine and are distant homologues of human SAMHD1. Our results suggest that bacterial defensive proteins deplete specific deoxynucleotides (either dCTP or dGTP) from the nucleotide pool during phage infection, thus starving the phage of an essential DNA building block and halting its replication. Our study shows that manipulation of the dNTP pool is a potent antiviral strategy shared by both prokaryotes and eukaryotes..\n",
+ "Sensor": "Host integrity monitoring",
+ "Activator": "Unknown",
+ "Effector": "Nucleotide modifying",
+ "PFAM": [
+ {
+ "ID": "dCMP_cyt_deam_1",
+ "DE": "Cytidine and deoxycytidylate deaminase zinc-binding region",
+ "GA": "25; 25;",
+ "TP": "Domain",
+ "ML": 102,
+ "CL": "CL0109",
+ "NE": "",
+ "AC": "PF00383"
+ },
+ {
+ "ID": "MafB19-deam",
+ "DE": "MafB19-like deaminase",
+ "GA": "27; 27;",
+ "TP": "Family",
+ "ML": 144,
+ "CL": "CL0109",
+ "NE": "",
+ "AC": "PF14437"
+ }
+ ]
+ },
+ {
+ "title": "Dsr",
+ "doi": "10.1126/science.aba0372",
+ "abstract": "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.\n",
+ "Sensor": "Sensing phage protein",
+ "Activator": "Direct",
+ "Effector": "Nucleotide modifying",
+ "PFAM": [
+ {
+ "ID": "SIR2_2",
+ "DE": "SIR2-like domain",
+ "GA": "24.5; 24.5;",
+ "TP": "Family",
+ "ML": 142,
+ "CL": "CL0063",
+ "NE": "",
+ "AC": "PF13289"
+ }
+ ]
+ },
+ {
+ "title": "Mok_Hok_Sok",
+ "relevantAbstracts": [
+ {
+ "doi": "10.1128/jb.178.7.2044-2050.1996"
+ },
+ {
+ "doi": "10.1016/0022-2836(92)90714-u"
+ }
+ ],
+ "contributors": [
+ "Jean Cury"
+ ],
+ "doi": "10.1128/jb.178.7.2044-2050.1996",
+ "abstract": "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 ...\n",
+ "Sensor": "Monitoring of the host cell machinery (?)",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "HOK_GEF",
+ "DE": "Hok/gef family",
+ "GA": "22; 22;",
+ "TP": "Family",
+ "ML": 42,
+ "CL": "",
+ "NE": "",
+ "AC": "PF01848"
+ }
+ ]
+ },
+ {
+ "title": "Gao_Qat",
+ "doi": "10.1126/science.aba0372",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "TatD_DNase",
+ "DE": "TatD related DNase",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 253,
+ "CL": "CL0036",
+ "NE": "",
+ "AC": "PF01026"
+ },
+ {
+ "ID": "KAP_NTPase",
+ "DE": "KAP family P-loop domain",
+ "GA": "20; 18;",
+ "TP": "Domain",
+ "ML": 293,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF07693"
+ }
+ ]
+ },
+ {
+ "title": "Nhi",
+ "contributors": [
+ "Alba Herrero del Valle"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1016/j.chom.2022.03.001"
+ },
+ {
+ "doi": "10.1016/j.chom.2022.09.017"
+ }
+ ],
+ "doi": "10.1016/j.chom.2022.03.001",
+ "abstract": "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.\n",
+ "Sensor": "Phage protein sensing",
+ "Activator": "Direct binding",
+ "Effector": "Nucleic acid degrading",
+ "PFAM": [
+ {
+ "ID": "Viral_helicase1",
+ "DE": "Viral (Superfamily 1) RNA helicase",
+ "GA": "21; 21;",
+ "TP": "Family",
+ "ML": 228,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF01443"
+ },
+ {
+ "ID": "SLFN-g3_helicase",
+ "DE": "Schlafen group 3, DNA/RNA helicase domain",
+ "GA": "20.3; 20.3;",
+ "TP": "Domain",
+ "ML": 355,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF09848"
+ },
+ {
+ "ID": "AAA_30",
+ "DE": "AAA domain",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 191,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13604"
+ }
+ ]
+ },
+ {
+ "title": "PsyrTA",
+ "contributors": [
+ "Ernest Mordret"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1016/j.chom.2022.09.017"
+ },
+ {
+ "doi": "10.1016/j.molcel.2013.02.002"
+ },
+ {
+ "doi": "10.1371/journal.ppat.1005317"
+ }
+ ],
+ "doi": "10.1016/j.chom.2022.09.017",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "DEAD",
+ "DE": "DEAD/DEAH box helicase",
+ "GA": "26; 24.1;",
+ "TP": "Domain",
+ "ML": 166,
+ "CL": "CL0023",
+ "NE": "SPRY",
+ "AC": "PF00270"
+ },
+ {
+ "ID": "Helicase_C",
+ "DE": "Helicase conserved C-terminal domain",
+ "GA": "23.5; 23.5;",
+ "TP": "Domain",
+ "ML": 110,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF00271"
+ },
+ {
+ "ID": "DNA_processg_A",
+ "DE": "DNA recombination-mediator protein A",
+ "GA": "29.6; 29.6;",
+ "TP": "Family",
+ "ML": 211,
+ "CL": "CL0349",
+ "NE": "",
+ "AC": "PF02481"
+ },
+ {
+ "ID": "ResIII",
+ "DE": "Type III restriction enzyme, res subunit",
+ "GA": "22.5; 22.5;",
+ "TP": "Family",
+ "ML": 164,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF04851"
+ },
+ {
+ "ID": "LDcluster4",
+ "DE": "SLOG cluster4 family",
+ "GA": "26.3; 26.3;",
+ "TP": "Family",
+ "ML": 152,
+ "CL": "CL0349",
+ "NE": "",
+ "AC": "PF18306"
+ }
+ ]
+ },
+ {
+ "title": "SpbK",
+ "doi": "10.1371/journal.pgen.1010065",
+ "abstract": "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 SP\u00c3\u0178 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 SP\u00c3\u0178, likely providing selective pressure for the maintenance of ICEBs1 in B. subtilis. A single gene in ICEBs1 (yddK, now called spbK for SP\u00c3\u0178 killing) was both necessary and sufficient for this protection. spbK inhibited production of SP\u00c3\u0178, during both activation of a lysogen and following de novo infection. We found that expression spbK, together with the SP\u00c3\u0178 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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "TIR_2",
+ "DE": "TIR domain",
+ "GA": "28; 28;",
+ "TP": "Domain",
+ "ML": 122,
+ "CL": "CL0173",
+ "NE": "",
+ "AC": "PF13676"
+ }
+ ]
+ },
+ {
+ "title": "Mokosh",
+ "contributors": [
+ "Marian Dominguez-Mirazo"
+ ],
+ "relevantAbstract": [
+ {
+ "doi": "10.1016/j.chom.2022.09.017"
+ },
+ {
+ "doi": "10.1101/2022.12.12.520048"
+ }
+ ],
+ "doi": "10.1016/j.chom.2022.09.017",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "Pkinase",
+ "DE": "Protein kinase domain",
+ "GA": "31.7; 31.7;",
+ "TP": "Domain",
+ "ML": 263,
+ "CL": "CL0016",
+ "NE": "",
+ "AC": "PF00069"
+ },
+ {
+ "ID": "PK_Tyr_Ser-Thr",
+ "DE": "Protein tyrosine and serine/threonine kinase",
+ "GA": "23.1; 23.1;",
+ "TP": "Domain",
+ "ML": 258,
+ "CL": "CL0016",
+ "NE": "",
+ "AC": "PF07714"
+ },
+ {
+ "ID": "NERD",
+ "DE": "Nuclease-related domain",
+ "GA": "22.1; 22.1;",
+ "TP": "Family",
+ "ML": 111,
+ "CL": "CL0236",
+ "NE": "",
+ "AC": "PF08378"
+ },
+ {
+ "ID": "AAA_11",
+ "DE": "AAA domain",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 257,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13086"
+ },
+ {
+ "ID": "AAA_12",
+ "DE": "AAA domain",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 195,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13087"
+ },
+ {
+ "ID": "PLDc_2",
+ "DE": "PLD-like domain",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 132,
+ "CL": "CL0479",
+ "NE": "",
+ "AC": "PF13091"
+ },
+ {
+ "ID": "AAA_19",
+ "DE": "AAA domain",
+ "GA": "25.1; 25.1;",
+ "TP": "Domain",
+ "ML": 135,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13245"
+ },
+ {
+ "ID": "AAA_30",
+ "DE": "AAA domain",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 191,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13604"
+ }
+ ]
+ },
+ {
+ "title": "dGTPase",
+ "contributors": [
+ "Aude Bernheim"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1038/s41564-022-01158-0"
+ }
+ ],
+ "doi": "10.1038/s41564-022-01158-0",
+ "abstract": "DNA viruses and retroviruses consume large quantities of deoxynucleotides (dNTPs) when replicating. The human antiviral factor SAMHD1 takes advantage of this vulnerability in the viral lifecycle, and inhibits viral replication by degrading dNTPs into their constituent deoxynucleosides and inorganic phosphate. Here, we report that bacteria use a similar strategy to defend against bacteriophage infection. We identify a family of defensive bacterial deoxycytidine triphosphate (dCTP) deaminase proteins that convert dCTP into deoxyuracil nucleotides in response to phage infection. We also identify a family of phage resistance genes that encode deoxyguanosine triphosphatase (dGTPase) enzymes, which degrade dGTP into phosphate-free deoxyguanosine and are distant homologues of human SAMHD1. Our results suggest that bacterial defensive proteins deplete specific deoxynucleotides (either dCTP or dGTP) from the nucleotide pool during phage infection, thus starving the phage of an essential DNA building block and halting its replication. Our study shows that manipulation of the dNTP pool is a potent antiviral strategy shared by both prokaryotes and eukaryotes.\n",
+ "Sensor": "Monitoring of the host cell machinery integrity",
+ "Activator": "Direct",
+ "Effector": "Nucleotide modifying",
+ "PFAM": [
+ {
+ "ID": "HD",
+ "DE": "HD domain",
+ "GA": "22; 22;",
+ "TP": "Family",
+ "ML": 116,
+ "CL": "CL0237",
+ "NE": "",
+ "AC": "PF01966"
+ },
+ {
+ "ID": "HD_assoc",
+ "DE": "Phosphohydrolase-associated domain",
+ "GA": "22.2; 22.2;",
+ "TP": "Domain",
+ "ML": 91,
+ "CL": "",
+ "NE": "",
+ "AC": "PF13286"
+ }
+ ]
+ },
+ {
+ "title": "AbiJ",
+ "doi": "10.1016/j.mib.2005.06.006",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "Abi_C",
+ "DE": "Abortive infection C-terminus",
+ "GA": "24; 24;",
+ "TP": "Family",
+ "ML": 83,
+ "CL": "",
+ "NE": "",
+ "AC": "PF14355"
+ }
+ ]
+ },
+ {
+ "title": "Gao_Mza",
+ "contributors": [
+ "Hugo Vaysset"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1126/science.aba0372"
+ }
+ ],
+ "doi": "10.1126/science.aba0372",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "Ank",
+ "DE": "Ankyrin repeat",
+ "GA": "21.1; 14.7;",
+ "TP": "Repeat",
+ "ML": 33,
+ "CL": "CL0465",
+ "NE": "",
+ "AC": "PF00023"
+ },
+ {
+ "ID": "Sigma70_r2",
+ "DE": "Sigma-70 region 2",
+ "GA": "24; 24;",
+ "TP": "Domain",
+ "ML": 71,
+ "CL": "CL0123",
+ "NE": "",
+ "AC": "PF04542"
+ },
+ {
+ "ID": "Sigma70_r4",
+ "DE": "Sigma-70, region 4",
+ "GA": "24.1; 24.1;",
+ "TP": "Domain",
+ "ML": 50,
+ "CL": "CL0123",
+ "NE": "",
+ "AC": "PF04545"
+ },
+ {
+ "ID": "AIPR",
+ "DE": "AIPR protein",
+ "GA": "25; 25;",
+ "TP": "Family",
+ "ML": 307,
+ "CL": "",
+ "NE": "",
+ "AC": "PF10592"
+ },
+ {
+ "ID": "Z1",
+ "DE": "Z1 domain",
+ "GA": "25; 25;",
+ "TP": "Domain",
+ "ML": 227,
+ "CL": "",
+ "NE": "",
+ "AC": "PF10593"
+ },
+ {
+ "ID": "HATPase_c_3",
+ "DE": "Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase",
+ "GA": "25; 25;",
+ "TP": "Domain",
+ "ML": 137,
+ "CL": "CL0025",
+ "NE": "",
+ "AC": "PF13589"
+ },
+ {
+ "ID": "Ank_3",
+ "DE": "Ankyrin repeat",
+ "GA": "22.3; 17.2;",
+ "TP": "Repeat",
+ "ML": 30,
+ "CL": "CL0465",
+ "NE": "",
+ "AC": "PF13606"
+ },
+ {
+ "ID": "DUF4420",
+ "DE": "Putative PD-(D/E)XK family member, (DUF4420)",
+ "GA": "27; 27;",
+ "TP": "Family",
+ "ML": 306,
+ "CL": "CL0236",
+ "NE": "",
+ "AC": "PF14390"
+ }
+ ]
+ },
+ {
+ "title": "DRT",
+ "contributors": [
+ "Helena Shomar",
+ "Marie Guillaume"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1093/nar/gkac467"
+ },
+ {
+ "doi": "10.1126/science.aba0372"
+ }
+ ],
+ "doi": "10.1126/science.aba0372",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "RVT_1",
+ "DE": "Reverse transcriptase (RNA-dependent DNA polymerase)",
+ "GA": "29.6; 29.6;",
+ "TP": "Domain",
+ "ML": 205,
+ "CL": "CL0027",
+ "NE": "",
+ "AC": "PF00078"
+ }
+ ]
+ },
+ {
+ "title": "SanaTA",
+ "contributors": [
+ "Alba Herrero del Valle"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1016/j.molcel.2013.02.002"
+ }
+ ],
+ "doi": "10.1016/j.molcel.2013.02.002",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "AbiEii",
+ "DE": "Nucleotidyl transferase AbiEii toxin, Type IV TA system",
+ "GA": "22.5; 22.5;",
+ "TP": "Domain",
+ "ML": 238,
+ "CL": "CL0260",
+ "NE": "",
+ "AC": "PF08843"
+ }
+ ]
+ },
+ {
+ "title": "Thoeris",
+ "doi": "10.1126/science.aar4120",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Signaling",
+ "Effector": "Nucleotide modifying",
+ "PFAM": [
+ {
+ "ID": "ThsB_TIR",
+ "DE": "Thoeris protein ThsB, TIR-like domain",
+ "GA": "21.2; 21.2;",
+ "TP": "Domain",
+ "ML": 130,
+ "CL": "CL0173",
+ "NE": "",
+ "AC": "PF08937"
+ },
+ {
+ "ID": "SIR2_2",
+ "DE": "SIR2-like domain",
+ "GA": "24.5; 24.5;",
+ "TP": "Family",
+ "ML": 142,
+ "CL": "CL0063",
+ "NE": "",
+ "AC": "PF13289"
+ },
+ {
+ "ID": "STALD",
+ "DE": "Sir2- and TIR-associating SLOG family",
+ "GA": "25.7; 25.7;",
+ "TP": "Family",
+ "ML": 208,
+ "CL": "CL0349",
+ "NE": "",
+ "AC": "PF18185"
+ }
+ ]
+ },
+ {
+ "title": "Dnd",
+ "doi": "10.1038/nchembio.2007.39",
+ "abstract": "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.\n",
+ "Sensor": "Detecting invading nucleic acid",
+ "Activator": "Unknown",
+ "Effector": "Nucleic acid degrading",
+ "PFAM": [
+ {
+ "ID": "Aminotran_5",
+ "DE": "Aminotransferase class-V",
+ "GA": "21.5; 21.5;",
+ "TP": "Domain",
+ "ML": 371,
+ "CL": "CL0061",
+ "NE": "",
+ "AC": "PF00266"
+ },
+ {
+ "ID": "PAPS_reduct",
+ "DE": "Phosphoadenosine phosphosulfate reductase family",
+ "GA": "22.5; 22.5;",
+ "TP": "Family",
+ "ML": 175,
+ "CL": "CL0039",
+ "NE": "",
+ "AC": "PF01507"
+ },
+ {
+ "ID": "DUF87",
+ "DE": "Helicase HerA, central domain",
+ "GA": "23.2; 23.2;",
+ "TP": "Domain",
+ "ML": 220,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF01935"
+ },
+ {
+ "ID": "DndE",
+ "DE": "DNA sulphur modification protein DndE",
+ "GA": "25; 25;",
+ "TP": "Domain",
+ "ML": 111,
+ "CL": "CL0057",
+ "NE": "",
+ "AC": "PF08870"
+ },
+ {
+ "ID": "AAA_23",
+ "DE": "AAA domain",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 201,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13476"
+ },
+ {
+ "ID": "DndB",
+ "DE": "DNA-sulfur modification-associated",
+ "GA": "29.1; 29.1;",
+ "TP": "Family",
+ "ML": 339,
+ "CL": "",
+ "NE": "",
+ "AC": "PF14072"
+ }
+ ]
+ },
+ {
+ "title": "PD-Lambda-2",
+ "doi": "10.1038/s41564-022-01219-4",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "Peptidase_M78",
+ "DE": "IrrE N-terminal-like domain",
+ "GA": "22; 22;",
+ "TP": "Family",
+ "ML": 123,
+ "CL": "CL0126",
+ "NE": "",
+ "AC": "PF06114"
+ },
+ {
+ "ID": "HigB_toxin",
+ "DE": "HigB_toxin, RelE-like toxic component of a toxin-antitoxin system",
+ "GA": "27; 27;",
+ "TP": "Family",
+ "ML": 74,
+ "CL": "",
+ "NE": "",
+ "AC": "PF09907"
+ },
+ {
+ "ID": "Beta_protein",
+ "DE": "Beta protein",
+ "GA": "27; 27;",
+ "TP": "Family",
+ "ML": 345,
+ "CL": "",
+ "NE": "",
+ "AC": "PF14350"
+ }
+ ]
+ },
+ {
+ "title": "Rst_RT-nitrilase-Tm",
+ "doi": "10.1016/j.chom.2022.02.018",
+ "abstract": "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.\u00a0coli 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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "RVT_1",
+ "DE": "Reverse transcriptase (RNA-dependent DNA polymerase)",
+ "GA": "29.6; 29.6;",
+ "TP": "Domain",
+ "ML": 205,
+ "CL": "CL0027",
+ "NE": "",
+ "AC": "PF00078"
+ }
+ ]
+ },
+ {
+ "title": "FS_Sma",
+ "doi": "10.1016/j.cell.2022.07.014",
+ "abstract": "Bacteria encode sophisticated anti-phage systems that are diverse and versatile and display high genetic mobility. How this variability and mobility occurs remains largely unknown. Here, we demonstrate that a widespread family of pathogenicity islands, the phage-inducible chromosomal islands (PICIs), carry an impressive arsenal of defense mechanisms, which can be disseminated intra- and inter-generically by helper phages. These defense systems provide broad immunity, blocking not only phage reproduction, but also plasmid and non-cognate PICI transfer. Our results demonstrate that phages can mobilize PICI-encoded immunity systems to use them against other mobile genetic elements, which compete with the phages for the same bacterial hosts. Therefore, despite the cost, mobilization of PICIs may be beneficial for phages, PICIs, and bacteria in nature. Our results suggest that PICIs are important players controlling horizontal gene transfer and that PICIs and phages establish mutualistic interactions that drive bacterial ecology and evolution.\n",
+ "PFAM": [
+ {
+ "ID": "PemK_toxin",
+ "DE": "PemK-like, MazF-like toxin of type II toxin-antitoxin system",
+ "GA": "23.1; 23.1;",
+ "TP": "Domain",
+ "ML": 109,
+ "CL": "CL0010",
+ "NE": "",
+ "AC": "PF02452"
+ }
+ ]
+ },
+ {
+ "title": "Gao_RL",
+ "contributors": [
+ "Aude Bernheim"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1126/science.aba0372"
+ }
+ ],
+ "doi": "10.1126/science.aba0372",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "SNF2-rel_dom",
+ "DE": "SNF2-related domain",
+ "GA": "23.9; 23.9;",
+ "TP": "Domain",
+ "ML": 290,
+ "CL": "CL0023",
+ "NE": "Bromodomain",
+ "AC": "PF00176"
+ },
+ {
+ "ID": "Helicase_C",
+ "DE": "Helicase conserved C-terminal domain",
+ "GA": "23.5; 23.5;",
+ "TP": "Domain",
+ "ML": 110,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF00271"
+ },
+ {
+ "ID": "DUF499",
+ "DE": "Protein of unknown function (DUF499)",
+ "GA": "23; 23;",
+ "TP": "Family",
+ "ML": 1024,
+ "CL": "",
+ "NE": "",
+ "AC": "PF04465"
+ },
+ {
+ "ID": "ResIII",
+ "DE": "Type III restriction enzyme, res subunit",
+ "GA": "22.5; 22.5;",
+ "TP": "Family",
+ "ML": 164,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF04851"
+ },
+ {
+ "ID": "DUF1156",
+ "DE": "Protein of unknown function (DUF1156)",
+ "GA": "24; 24;",
+ "TP": "Family",
+ "ML": 73,
+ "CL": "",
+ "NE": "",
+ "AC": "PF06634"
+ },
+ {
+ "ID": "DUF3780",
+ "DE": "Protein of unknown function (DUF3780)",
+ "GA": "27; 27;",
+ "TP": "Family",
+ "ML": 184,
+ "CL": "",
+ "NE": "",
+ "AC": "PF12635"
+ },
+ {
+ "ID": "PLDc_2",
+ "DE": "PLD-like domain",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 132,
+ "CL": "CL0479",
+ "NE": "",
+ "AC": "PF13091"
+ },
+ {
+ "ID": "Fn3_assoc",
+ "DE": "Fn3 associated",
+ "GA": "23; 23;",
+ "TP": "Domain",
+ "ML": 59,
+ "CL": "CL0159",
+ "NE": "",
+ "AC": "PF13287"
+ },
+ {
+ "ID": "CHB_HEX_C_1",
+ "DE": "Chitobiase/beta-hexosaminidase C-terminal domain",
+ "GA": "22; 22;",
+ "TP": "Domain",
+ "ML": 67,
+ "CL": "CL0159",
+ "NE": "",
+ "AC": "PF13290"
+ }
+ ]
+ },
+ {
+ "title": "MazEF",
+ "doi": "10.1007/s00438-004-1048-y",
+ "abstract": "The Escherichia coli gene pair mazEF is a regulatable chromosomal toxin-antitoxin module: mazF encodes a stable toxin and mazE encodes for a labile antitoxin that overcomes the lethal effect of MazF. Because MazE is labile, inhibition of mazE expression results in cell death. We studied the effect of mazEF on the development of bacteriophage P1 upon thermoinduction of the prophage P1CM c1ts and upon infection with virulent phage particles (P1vir). In several E. coli strains, we showed that the ?mazEF derivative strains produced significantly more phages than did the parent strain. In addition, upon induction of K38(P1CM c1ts), nearly all of the ?mazEF mutant cells lysed; in contrast, very few of the parental mazEF + K38 cells underwent lysis. However, most of these cells did not remain viable. Thus, while the ?mazEF cells die as a result of the lytic action of the phage, most of the mazEF + cells are killed by a different mechanism, apparently through the action of the chromosomal mazEF system itself. Furthermore, the introduction of lysogens into a growing non-lysogenic culture is lethal to ?mazEF but not for mazEF + cultures. Thus, although mazEF action causes individual cells to die, upon phage growth this is generally beneficial to the bacterial culture because it causes P1 phage exclusion from the bacterial population. These results provide additional support for the view that bacterial cultures may share some of the characteristics of multicellular organisms.\n",
+ "PFAM": [
+ {
+ "ID": "PemK_toxin",
+ "DE": "PemK-like, MazF-like toxin of type II toxin-antitoxin system",
+ "GA": "23.1; 23.1;",
+ "TP": "Domain",
+ "ML": 109,
+ "CL": "CL0010",
+ "NE": "",
+ "AC": "PF02452"
+ },
+ {
+ "ID": "MazE_antitoxin",
+ "DE": "Antidote-toxin recognition MazE, bacterial antitoxin",
+ "GA": "24.7; 24.7;",
+ "TP": "Domain",
+ "ML": 47,
+ "CL": "CL0132",
+ "NE": "",
+ "AC": "PF04014"
+ }
+ ]
+ },
+ {
+ "title": "AbiA",
+ "relevantAbstracts": [
+ {
+ "doi": "10.1023/A:1002027321171"
+ },
+ {
+ "doi": "10.1016/j.mib.2005.06.006"
+ },
+ {
+ "doi": "10.1093/nar/gkac467"
+ }
+ ],
+ "doi": "10.1016/j.mib.2005.06.006",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "RVT_1",
+ "DE": "Reverse transcriptase (RNA-dependent DNA polymerase)",
+ "GA": "29.6; 29.6;",
+ "TP": "Domain",
+ "ML": 205,
+ "CL": "CL0027",
+ "NE": "",
+ "AC": "PF00078"
+ },
+ {
+ "ID": "SLATT_5",
+ "DE": "SMODS and SLOG-associating 2TM effector domain family 5",
+ "GA": "29.5; 29.5;",
+ "TP": "Domain",
+ "ML": 191,
+ "CL": "CL0676",
+ "NE": "",
+ "AC": "PF18160"
+ },
+ {
+ "ID": "HEPN_AbiA_CTD",
+ "DE": "HEPN like, Abia C-terminal domain",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 132,
+ "CL": "CL0291",
+ "NE": "",
+ "AC": "PF18732"
+ }
+ ]
+ },
+ {
+ "title": "Lit",
+ "contributors": [
+ "Lucas Paoli"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1128/jb.169.3.1232-1238.1987"
+ },
+ {
+ "doi": "10.1128/jb.170.5.2056-2062.1988"
+ },
+ {
+ "doi": "10.1073/pnas.91.2.802"
+ },
+ {
+ "doi": "10.1074/jbc.M002546200"
+ },
+ {
+ "doi": "10.1186/1743-422X-7-360"
+ }
+ ],
+ "doi": "10.1073/pnas.91.2.802",
+ "abstract": "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.\n",
+ "Sensor": "Monitoring host integrity",
+ "Activator": "Direct",
+ "Effector": "Other (Cleaves an elongation factor, inhibiting cellular translation",
+ "PFAM": [
+ {
+ "ID": "Peptidase_U49",
+ "DE": "Peptidase U49",
+ "GA": "23.9; 23.9;",
+ "TP": "Family",
+ "ML": 202,
+ "CL": "CL0126",
+ "NE": "",
+ "AC": "PF10463"
+ }
+ ]
+ },
+ {
+ "title": "JukAB",
+ "doi": "10.1101/2022.09.17.508391",
+ "abstract": "Jumbo bacteriophages of the ?KZ-like family are characterized by large genomes (>200 kb) and the remarkable ability to assemble a proteinaceous nucleus-like structure. The nucleus protects the phage genome from canonical DNA-targeting immune systems, such as CRISPR-Cas and restriction-modification. We hypothesized that the failure of common bacterial defenses creates selective pressure for immune systems that target the unique jumbo phage biology. Here, we identify the \"jumbo phage killer\"(Juk) immune system that is deployed by a clinical isolate of Pseudomonas aeruginosa to resist PhiKZ. Juk immunity rescues the cell by preventing early phage transcription, DNA replication, and nucleus assembly. Phage infection is first sensed by JukA (formerly YaaW), which localizes rapidly to the site of phage infection at the cell pole, triggered by ejected phage factors. The effector protein JukB is recruited by JukA, which is required to enable immunity and the subsequent degradation of the phage DNA. JukA homologs are found in several bacterial phyla and are associated with numerous other putative effectors, many of which provided specific antiPhiKZ activity when expressed in P. aeruginosa. Together, these data reveal a novel strategy for immunity whereby immune factors are recruited to the site of phage protein and DNA ejection to prevent phage progression and save the cell.\n",
+ "PFAM": [
+ {
+ "ID": "DUF3944",
+ "DE": "Domain of unknown function (DUF3944)",
+ "GA": "24; 24;",
+ "TP": "Domain",
+ "ML": 35,
+ "CL": "",
+ "NE": "",
+ "AC": "PF13099"
+ }
+ ]
+ },
+ {
+ "title": "AbiU",
+ "contributors": [
+ "Nathalie Bechon"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1023/A:1002027321171"
+ },
+ {
+ "doi": "10.1016/j.mib.2005.06.006"
+ },
+ {
+ "doi": "10.1128/AEM.67.11.5225-5232.2001"
+ }
+ ],
+ "doi": "10.1128/AEM.67.11.5225-5232.2001",
+ "abstract": "This study reports on the identification and characterization of a novel abortive infection system, AbiU, from Lactococcus lactis. AbiU confers resistance to phages from the three main industrially relevant lactococcal phage species: c2, 936, and P335. The presence of AbiU reduced the efficiency of plaquing against specific phage from each species as follows: 3.7 \u00d7 10\u22121, 1.0 \u00d7 10\u22122, and 1.0 \u00d7 10\u22121, respectively. abiU involves two open reading frames,abiU1 (1,772 bp) and abiU2 (1,019 bp). Evidence indicates that AbiU1 is responsible for phage resistance and that AbiU2 may downregulate phage resistance against 936 and P335 type phages but not c2 type phage. AbiU appeared to delay transcription of both phage 712 and c2, with the effect being more marked on phage c2.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "AIPR",
+ "DE": "AIPR protein",
+ "GA": "25; 25;",
+ "TP": "Family",
+ "ML": 307,
+ "CL": "",
+ "NE": "",
+ "AC": "PF10592"
+ }
+ ]
+ },
+ {
+ "title": "CapRel",
+ "doi": "10.1038/s41586-022-05444-z",
+ "abstract": "Bacteria have evolved diverse immunity mechanisms to protect themselves against the constant onslaught of bacteriophages. Similar to how eukaryotic innate immune systems sense foreign invaders through pathogen-associated molecular patterns4 (PAMPs), many bacterial immune systems that respond to bacteriophage infection require phage-specific triggers to be activated. However, the identities of such triggers and the sensing mechanisms remain largely unknown. Here we identify and investigate the anti-phage function of CapRelSJ46, a fused toxini-antitoxin system that protects Escherichia coli against diverse phages. Using genetic, biochemical and structural analyses, we demonstrate that the C-terminal domain of CapRelSJ46 regulates the toxic N-terminal region, serving as both antitoxin and phage infection sensor. Following infection by certain phages, newly synthesized major capsid protein binds directly to the C-terminal domain of CapRelSJ46 to relieve autoinhibition, enabling the toxin domain to pyrophosphorylate tRNAs, which blocks translation to restrict viral infection. Collectively, our results reveal the molecular mechanism by which a bacterial immune system directly senses a conserved, essential component of phages, suggesting a PAMP-like sensing model for toxin-antitoxin-mediated innate immunity in bacteria. We provide evidence that CapRels and their phage-encoded triggers are engaged in a \"Red Queen conflict\", revealing a new front in the intense coevolutionary battle between phages and bacteria. Given that capsid proteins of some eukaryotic viruses are known to stimulate innate immune signalling in mammalian hosts, our results reveal a deeply conserved facet of immunity.\n",
+ "Sensor": "Sensing of phage protein",
+ "Activator": "Direct",
+ "Effector": "Nucleic acid degrading (pyrophosphorylates tRNAs)",
+ "PFAM": [
+ {
+ "ID": "RelA_SpoT",
+ "DE": "Region found in RelA / SpoT proteins",
+ "GA": "27; 27;",
+ "TP": "Family",
+ "ML": 112,
+ "CL": "CL0260",
+ "NE": "",
+ "AC": "PF04607"
+ }
+ ]
+ },
+ {
+ "title": "BREX",
+ "contributors": [
+ "Marian Dominguez-Mirazo"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1093/nar/gkaa290"
+ },
+ {
+ "doi": "10.1093/nar/gky1125"
+ },
+ {
+ "doi": "10.15252/embj.201489455"
+ }
+ ],
+ "doi": "10.15252/embj.201489455",
+ "abstract": "The perpetual arms race between bacteria and phage has resulted in the evolution of efficient resistance systems that protect bacteria from phage infection. Such systems, which include the CRISPR-Cas and restriction-modification systems, have proven to be invaluable in the biotechnology and dairy industries. Here, we report on a six-gene cassette in Bacillus cereus which, when integrated into the Bacillus subtilis genome, confers resistance to a broad range of phages, including both virulent and temperate ones. This cassette includes a putative Lon-like protease, an alkaline phosphatase domain protein, a putative RNA-binding protein, a DNA methylase, an ATPase-domain protein, and a protein of unknown function. We denote this novel defense system BREX (Bacteriophage Exclusion) and show that it allows phage adsorption but blocks phage DNA replication. Furthermore, our results suggest that methylation on non-palindromic TAGGAG motifs in the bacterial genome guides self/non-self discrimination and is essential for the defensive function of the BREX system. However, unlike restriction-modification systems, phage DNA does not appear to be cleaved or degraded by BREX, suggesting a novel mechanism of defense. Pan genomic analysis revealed that BREX and BREX-like systems, including the distantly related Pgl system described in Streptomyces coelicolor, are widely distributed in ~10% of all sequenced microbial genomes and can be divided into six coherent subtypes in which the gene composition and order is conserved. Finally, we detected a phage family that evades the BREX defense, implying that anti-BREX mechanisms may have evolved in some phages as part of their arms race with bacteria.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "Pkinase",
+ "DE": "Protein kinase domain",
+ "GA": "31.7; 31.7;",
+ "TP": "Domain",
+ "ML": 263,
+ "CL": "CL0016",
+ "NE": "",
+ "AC": "PF00069"
+ },
+ {
+ "ID": "SNF2-rel_dom",
+ "DE": "SNF2-related domain",
+ "GA": "23.9; 23.9;",
+ "TP": "Domain",
+ "ML": 290,
+ "CL": "CL0023",
+ "NE": "Bromodomain",
+ "AC": "PF00176"
+ },
+ {
+ "ID": "DEAD",
+ "DE": "DEAD/DEAH box helicase",
+ "GA": "26; 24.1;",
+ "TP": "Domain",
+ "ML": 166,
+ "CL": "CL0023",
+ "NE": "SPRY",
+ "AC": "PF00270"
+ },
+ {
+ "ID": "Helicase_C",
+ "DE": "Helicase conserved C-terminal domain",
+ "GA": "23.5; 23.5;",
+ "TP": "Domain",
+ "ML": 110,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF00271"
+ },
+ {
+ "ID": "PAPS_reduct",
+ "DE": "Phosphoadenosine phosphosulfate reductase family",
+ "GA": "22.5; 22.5;",
+ "TP": "Family",
+ "ML": 175,
+ "CL": "CL0039",
+ "NE": "",
+ "AC": "PF01507"
+ },
+ {
+ "ID": "N6_N4_Mtase",
+ "DE": "DNA methylase",
+ "GA": "26.7; 26.7;",
+ "TP": "Family",
+ "ML": 221,
+ "CL": "CL0063",
+ "NE": "",
+ "AC": "PF01555"
+ },
+ {
+ "ID": "N6_Mtase",
+ "DE": "N-6 DNA Methylase",
+ "GA": "20.4; 20.4;",
+ "TP": "Family",
+ "ML": 311,
+ "CL": "CL0063",
+ "NE": "",
+ "AC": "PF02384"
+ },
+ {
+ "ID": "ResIII",
+ "DE": "Type III restriction enzyme, res subunit",
+ "GA": "22.5; 22.5;",
+ "TP": "Family",
+ "ML": 164,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF04851"
+ },
+ {
+ "ID": "Eco57I",
+ "DE": "Eco57I restriction-modification methylase",
+ "GA": "21.1; 21.1;",
+ "TP": "Domain",
+ "ML": 104,
+ "CL": "CL0063",
+ "NE": "",
+ "AC": "PF07669"
+ },
+ {
+ "ID": "PK_Tyr_Ser-Thr",
+ "DE": "Protein tyrosine and serine/threonine kinase",
+ "GA": "23.1; 23.1;",
+ "TP": "Domain",
+ "ML": 258,
+ "CL": "CL0016",
+ "NE": "",
+ "AC": "PF07714"
+ },
+ {
+ "ID": "NERD",
+ "DE": "Nuclease-related domain",
+ "GA": "22.1; 22.1;",
+ "TP": "Family",
+ "ML": 111,
+ "CL": "CL0236",
+ "NE": "",
+ "AC": "PF08378"
+ },
+ {
+ "ID": "PglZ",
+ "DE": "PglZ domain",
+ "GA": "25; 25;",
+ "TP": "Domain",
+ "ML": 179,
+ "CL": "CL0088",
+ "NE": "",
+ "AC": "PF08665"
+ },
+ {
+ "ID": "BrxB",
+ "DE": "BREX protein BrxB",
+ "GA": "26.8; 26.8;",
+ "TP": "Domain",
+ "ML": 124,
+ "CL": "",
+ "NE": "",
+ "AC": "PF08747"
+ },
+ {
+ "ID": "BrxA",
+ "DE": "BrxA",
+ "GA": "23; 23;",
+ "TP": "Family",
+ "ML": 184,
+ "CL": "CL0123",
+ "NE": "",
+ "AC": "PF08849"
+ },
+ {
+ "ID": "BrxC_BrxD",
+ "DE": "BREX system ATP-binding protein BrxC/D",
+ "GA": "22.2; 22.2;",
+ "TP": "Domain",
+ "ML": 414,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF10923"
+ },
+ {
+ "ID": "BrxL_ATPase",
+ "DE": "Lon-like protease BrxL-like, ATPase domain",
+ "GA": "25; 25;",
+ "TP": "Domain",
+ "ML": 313,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13337"
+ },
+ {
+ "ID": "MIT_C",
+ "DE": "Phospholipase D-like domain at C-terminus of MIT",
+ "GA": "25; 25;",
+ "TP": "Domain",
+ "ML": 142,
+ "CL": "CL0479",
+ "NE": "",
+ "AC": "PF16565"
+ }
+ ]
+ },
+ {
+ "title": "AbiK",
+ "doi": "10.1016/j.mib.2005.06.006",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "RVT_1",
+ "DE": "Reverse transcriptase (RNA-dependent DNA polymerase)",
+ "GA": "29.6; 29.6;",
+ "TP": "Domain",
+ "ML": 205,
+ "CL": "CL0027",
+ "NE": "",
+ "AC": "PF00078"
+ }
+ ]
+ },
+ {
+ "title": "RnlAB",
+ "doi": "10.1534/genetics.110.121798",
+ "abstract": "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.\n",
+ "Sensor": "Monitor the integrity of the bacterial cell machinery",
+ "Activator": "Direct",
+ "Effector": "Nucleic acid degrading",
+ "PFAM": [
+ {
+ "ID": "RnlB_antitoxin",
+ "DE": "Antitoxin to bacterial toxin RNase LS or RnlA",
+ "GA": "27; 27;",
+ "TP": "Family",
+ "ML": 94,
+ "CL": "",
+ "NE": "",
+ "AC": "PF15933"
+ },
+ {
+ "ID": "RnlA_toxin",
+ "DE": "RNase LS, bacterial toxin",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 87,
+ "CL": "",
+ "NE": "",
+ "AC": "PF15935"
+ },
+ {
+ "ID": "HEPN_RnaseLS",
+ "DE": "RnaseLS-like HEPN",
+ "GA": "29; 29;",
+ "TP": "Family",
+ "ML": 124,
+ "CL": "CL0291",
+ "NE": "",
+ "AC": "PF18869"
+ },
+ {
+ "ID": "RnlA-toxin_DBD",
+ "DE": "RNase LS, bacterial toxin DBD domain",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 125,
+ "CL": "CL0291",
+ "NE": "",
+ "AC": "PF19034"
+ }
+ ]
+ },
+ {
+ "title": "AbiR",
+ "doi": "10.1016/j.mib.2005.06.006",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "SNF2-rel_dom",
+ "DE": "SNF2-related domain",
+ "GA": "23.9; 23.9;",
+ "TP": "Domain",
+ "ML": 290,
+ "CL": "CL0023",
+ "NE": "Bromodomain",
+ "AC": "PF00176"
+ },
+ {
+ "ID": "Helicase_C",
+ "DE": "Helicase conserved C-terminal domain",
+ "GA": "23.5; 23.5;",
+ "TP": "Domain",
+ "ML": 110,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF00271"
+ },
+ {
+ "ID": "Sigma70_r4",
+ "DE": "Sigma-70, region 4",
+ "GA": "24.1; 24.1;",
+ "TP": "Domain",
+ "ML": 50,
+ "CL": "CL0123",
+ "NE": "",
+ "AC": "PF04545"
+ },
+ {
+ "ID": "ResIII",
+ "DE": "Type III restriction enzyme, res subunit",
+ "GA": "22.5; 22.5;",
+ "TP": "Family",
+ "ML": 164,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF04851"
+ },
+ {
+ "ID": "PLDc_2",
+ "DE": "PLD-like domain",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 132,
+ "CL": "CL0479",
+ "NE": "",
+ "AC": "PF13091"
+ }
+ ]
+ },
+ {
+ "title": "Rst_gop_beta_cll",
+ "doi": "10.1016/j.chom.2022.02.018",
+ "abstract": "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.\u00a0coli 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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "Beta_protein",
+ "DE": "Beta protein",
+ "GA": "27; 27;",
+ "TP": "Family",
+ "ML": 345,
+ "CL": "",
+ "NE": "",
+ "AC": "PF14350"
+ }
+ ]
+ },
+ {
+ "title": "Pif",
+ "contributors": [
+ "Lucas Paoli"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1007/BF00327934"
+ },
+ {
+ "doi": "10.1016/j.virol.2004.06.001"
+ },
+ {
+ "doi": "10.1128/jb.173.20.6507-6514.1991"
+ },
+ {
+ "doi": "10.1038/newbio231037a0"
+ }
+ ],
+ "doi": "10.1007/BF00327934",
+ "abstract": "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.\n",
+ "Sensor": "Sensing of phage protein",
+ "Activator": "Unknown",
+ "Effector": "Membrane disrupting (?)",
+ "PFAM": [
+ {
+ "ID": "KAP_NTPase",
+ "DE": "KAP family P-loop domain",
+ "GA": "20; 18;",
+ "TP": "Domain",
+ "ML": 293,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF07693"
+ }
+ ]
+ },
+ {
+ "title": "PD-T4-2",
+ "doi": "10.1038/s41564-022-01219-4",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "DUF262",
+ "DE": "Protein of unknown function DUF262",
+ "GA": "33.2; 33.2;",
+ "TP": "Family",
+ "ML": 199,
+ "CL": "CL0248",
+ "NE": "",
+ "AC": "PF03235"
+ },
+ {
+ "ID": "HEPN_RiboL-PSP",
+ "DE": "RiboL-PSP-HEPN",
+ "GA": "28.4; 28.4;",
+ "TP": "Domain",
+ "ML": 191,
+ "CL": "CL0291",
+ "NE": "",
+ "AC": "PF18735"
+ }
+ ]
+ },
+ {
+ "title": "SEFIR",
+ "contributors": [
+ "Helena Shomar",
+ "Marie Guillaume"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1016/j.chom.2022.09.017"
+ },
+ {
+ "doi": "10.1016/S0968-0004(03)00067-7"
+ }
+ ],
+ "doi": "10.1016/j.chom.2022.09.017",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "SEFIR",
+ "DE": "SEFIR domain",
+ "GA": "23; 23;",
+ "TP": "Family",
+ "ML": 150,
+ "CL": "CL0173",
+ "NE": "",
+ "AC": "PF08357"
+ },
+ {
+ "ID": "TIR_2",
+ "DE": "TIR domain",
+ "GA": "28; 28;",
+ "TP": "Domain",
+ "ML": 122,
+ "CL": "CL0173",
+ "NE": "",
+ "AC": "PF13676"
+ }
+ ]
+ },
+ {
+ "title": "PD-T4-4",
+ "contributors": [
+ "Nathalie Bechon"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1038/s41564-022-01219-4"
+ }
+ ],
+ "doi": "10.1038/s41564-022-01219-4",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "AAA_15",
+ "DE": "AAA ATPase domain",
+ "GA": "32.1; 32.1;",
+ "TP": "Domain",
+ "ML": 399,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13175"
+ },
+ {
+ "ID": "AAA_21",
+ "DE": "AAA domain, putative AbiEii toxin, Type IV TA system",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 304,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13304"
+ }
+ ]
+ },
+ {
+ "title": "Pycsar",
+ "doi": "10.1016/j.cell.2021.09.031",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Signaling molecules",
+ "Effector": "Membrane disrupting, Nucleotides modifying",
+ "PFAM": [
+ {
+ "ID": "AAA",
+ "DE": "ATPase family associated with various cellular activities (AAA)",
+ "GA": "21.2; 21.2;",
+ "TP": "Domain",
+ "ML": 131,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF00004"
+ },
+ {
+ "ID": "cNMP_binding",
+ "DE": "Cyclic nucleotide-binding domain",
+ "GA": "27.5; 27.5;",
+ "TP": "Domain",
+ "ML": 89,
+ "CL": "CL0029",
+ "NE": "",
+ "AC": "PF00027"
+ },
+ {
+ "ID": "Guanylate_cyc",
+ "DE": "Adenylate and Guanylate cyclase catalytic domain",
+ "GA": "21.9; 21.9;",
+ "TP": "Domain",
+ "ML": 183,
+ "CL": "CL0276",
+ "NE": "",
+ "AC": "PF00211"
+ },
+ {
+ "ID": "ThiF",
+ "DE": "ThiF family",
+ "GA": "28.1; 28.1;",
+ "TP": "Domain",
+ "ML": 219,
+ "CL": "CL0063",
+ "NE": "UBA_E1_SCCH",
+ "AC": "PF00899"
+ },
+ {
+ "ID": "Patatin",
+ "DE": "Patatin-like phospholipase",
+ "GA": "27.7; 27.7;",
+ "TP": "Family",
+ "ML": 191,
+ "CL": "CL0323",
+ "NE": "",
+ "AC": "PF01734"
+ },
+ {
+ "ID": "CAP12-PCTIR_TIR",
+ "DE": "CAP12/Pycsar effector protein, TIR domain",
+ "GA": "24.7; 24.7;",
+ "TP": "Domain",
+ "ML": 119,
+ "CL": "CL0173",
+ "NE": "",
+ "AC": "PF10137"
+ },
+ {
+ "ID": "Prok-E2_B",
+ "DE": "Prokaryotic E2 family B",
+ "GA": "25.4; 25.4;",
+ "TP": "Family",
+ "ML": 135,
+ "CL": "CL0208",
+ "NE": "",
+ "AC": "PF14461"
+ },
+ {
+ "ID": "Prok-JAB",
+ "DE": "Prokaryotic homologs of the JAB domain",
+ "GA": "25; 25;",
+ "TP": "Family",
+ "ML": 114,
+ "CL": "CL0366",
+ "NE": "",
+ "AC": "PF14464"
+ },
+ {
+ "ID": "SAVED",
+ "DE": "SMODS-associated and fused to various effectors sensor domain",
+ "GA": "26.2; 26.2;",
+ "TP": "Domain",
+ "ML": 189,
+ "CL": "",
+ "NE": "",
+ "AC": "PF18145"
+ },
+ {
+ "ID": "S_2TMBeta",
+ "DE": "SMODS-associating 2TM, beta-strand rich effector domain",
+ "GA": "31.2; 31.2;",
+ "TP": "Domain",
+ "ML": 181,
+ "CL": "",
+ "NE": "",
+ "AC": "PF18153"
+ },
+ {
+ "ID": "Saf_2TM",
+ "DE": "SAVED-fused 2TM effector domain",
+ "GA": "29.5; 29.5;",
+ "TP": "Domain",
+ "ML": 152,
+ "CL": "",
+ "NE": "",
+ "AC": "PF18303"
+ },
+ {
+ "ID": "PycTM",
+ "DE": "Pycsar effector protein",
+ "GA": "27.2; 27.2;",
+ "TP": "Family",
+ "ML": 107,
+ "CL": "",
+ "NE": "",
+ "AC": "PF18967"
+ }
+ ]
+ },
+ {
+ "title": "FS_HP_SDH_sah",
+ "doi": "10.1016/j.cell.2022.07.014",
+ "abstract": "Bacteria encode sophisticated anti-phage systems that are diverse and versatile and display high genetic mobility. How this variability and mobility occurs remains largely unknown. Here, we demonstrate that a widespread family of pathogenicity islands, the phage-inducible chromosomal islands (PICIs), carry an impressive arsenal of defense mechanisms, which can be disseminated intra- and inter-generically by helper phages. These defense systems provide broad immunity, blocking not only phage reproduction, but also plasmid and non-cognate PICI transfer. Our results demonstrate that phages can mobilize PICI-encoded immunity systems to use them against other mobile genetic elements, which compete with the phages for the same bacterial hosts. Therefore, despite the cost, mobilization of PICIs may be beneficial for phages, PICIs, and bacteria in nature. Our results suggest that PICIs are important players controlling horizontal gene transfer and that PICIs and phages establish mutualistic interactions that drive bacterial ecology and evolution.\n",
+ "PFAM": [
+ {
+ "ID": "SDH_sah",
+ "DE": "Serine dehydrogenase proteinase",
+ "GA": "20; 20;",
+ "TP": "Family",
+ "ML": 286,
+ "CL": "CL0127",
+ "NE": "",
+ "AC": "PF01972"
+ }
+ ]
+ },
+ {
+ "title": "Shedu",
+ "contributors": [
+ "Aude Bernheim"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1126/science.aar4120"
+ },
+ {
+ "doi": "10.1101/2023.08.10.552762"
+ },
+ {
+ "doi": "10.1101/2023.08.10.552793"
+ }
+ ],
+ "doi": "10.1126/science.aar4120",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "SduA_C",
+ "DE": "Shedu protein SduA, C-terminal",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 160,
+ "CL": "CL0236",
+ "NE": "",
+ "AC": "PF14082"
+ }
+ ]
+ },
+ {
+ "title": "Stk2",
+ "doi": "10.1016/j.chom.2016.08.010",
+ "abstract": "Organisms from all domains of life are infected by\u00a0viruses. 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.\n",
+ "Sensor": "Sensing of phage protein",
+ "Activator": "Direct",
+ "Effector": "Other (protein modifying)",
+ "PFAM": [
+ {
+ "ID": "Pkinase",
+ "DE": "Protein kinase domain",
+ "GA": "31.7; 31.7;",
+ "TP": "Domain",
+ "ML": 263,
+ "CL": "CL0016",
+ "NE": "",
+ "AC": "PF00069"
+ },
+ {
+ "ID": "PK_Tyr_Ser-Thr",
+ "DE": "Protein tyrosine and serine/threonine kinase",
+ "GA": "23.1; 23.1;",
+ "TP": "Domain",
+ "ML": 258,
+ "CL": "CL0016",
+ "NE": "",
+ "AC": "PF07714"
+ }
+ ]
+ },
+ {
+ "title": "SspBCDE",
+ "doi": "10.1128/mBio.00613-21",
+ "abstract": "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.\n",
+ "Sensor": "Detecting invading nucleic acid",
+ "Activator": "Direct",
+ "Effector": "Nucleic acid degrading",
+ "PFAM": [
+ {
+ "ID": "PAPS_reduct",
+ "DE": "Phosphoadenosine phosphosulfate reductase family",
+ "GA": "22.5; 22.5;",
+ "TP": "Family",
+ "ML": 175,
+ "CL": "CL0039",
+ "NE": "",
+ "AC": "PF01507"
+ },
+ {
+ "ID": "FtsK_SpoIIIE",
+ "DE": "FtsK/SpoIIIE family",
+ "GA": "24; 24;",
+ "TP": "Domain",
+ "ML": 221,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF01580"
+ },
+ {
+ "ID": "DUF262",
+ "DE": "Protein of unknown function DUF262",
+ "GA": "33.2; 33.2;",
+ "TP": "Family",
+ "ML": 199,
+ "CL": "CL0248",
+ "NE": "",
+ "AC": "PF03235"
+ },
+ {
+ "ID": "DUF1524",
+ "DE": "Protein of unknown function (DUF1524)",
+ "GA": "23; 23;",
+ "TP": "Domain",
+ "ML": 139,
+ "CL": "CL0263",
+ "NE": "",
+ "AC": "PF07510"
+ },
+ {
+ "ID": "DUF4007",
+ "DE": "Protein of unknown function (DUF4007)",
+ "GA": "27; 27;",
+ "TP": "Family",
+ "ML": 288,
+ "CL": "",
+ "NE": "",
+ "AC": "PF13182"
+ }
+ ]
+ },
+ {
+ "title": "NLR",
+ "doi": "10.1101/2022.07.19.500537",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "NACHT",
+ "DE": "NACHT domain",
+ "GA": "26.7; 26.7;",
+ "TP": "Domain",
+ "ML": 167,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF05729"
+ }
+ ]
+ },
+ {
+ "title": "Aditi",
+ "doi": "10.1016/j.chom.2022.09.017",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "DUF5677",
+ "DE": "Family of unknown function (DUF5677)",
+ "GA": "27.1; 27.1;",
+ "TP": "Family",
+ "ML": 166,
+ "CL": "",
+ "NE": "",
+ "AC": "PF18928"
+ }
+ ]
+ },
+ {
+ "title": "Old_exonuclease",
+ "contributors": [
+ "Marian Dominguez-Mirazo"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1128/jb.177.3.497-501.1995"
+ },
+ {
+ "doi": "10.1128/jb.177.3.497-501.1995"
+ }
+ ],
+ "doi": "10.1128/jb.177.3.497-501.1995",
+ "abstract": "The Old protein of bacteriophage P2 is responsible for interference with the growth of phage lambda and for killing of recBC mutant Escherichia coli. We have purified Old fused to the maltose-binding protein to 95% purity and characterized its enzymatic properties. The Old protein fused to maltose-binding protein has exonuclease activity on double-stranded DNA as well as nuclease activity on single-stranded DNA and RNA. The direction of digestion of double-stranded DNA is from 5' to 3', and digestion initiates at either the 5'-phosphoryl or 5'-hydroxyl terminus. The nuclease is active on nicked circular DNA, degrades DNA in a processive manner, and releases 5'-phosphoryl mononucleotides.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Nucleic acid degrading",
+ "PFAM": [
+ {
+ "ID": "AAA_15",
+ "DE": "AAA ATPase domain",
+ "GA": "32.1; 32.1;",
+ "TP": "Domain",
+ "ML": 399,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13175"
+ },
+ {
+ "ID": "AAA_21",
+ "DE": "AAA domain, putative AbiEii toxin, Type IV TA system",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 304,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13304"
+ }
+ ]
+ },
+ {
+ "title": "CARD_NLR",
+ "contributors": [
+ "Marian Dominguez-Mirazo"
+ ],
+ "relevantAbstract": [
+ {
+ "doi": "10.1101/2023.05.28.542683"
+ }
+ ],
+ "doi": "10.1101/2023.05.28.542683",
+ "abstract": "Caspase recruitment domains (CARDs) and pyrin domains are important facilitators of inflammasome activity and pyroptosis. Upon pathogen recognition by NLR proteins, CARDs recruit and activate caspases, which, in turn, activate gasdermin pore forming proteins to and induce pyroptotic cell death. Here we show that CARD-like domains are present in defense systems that protect bacteria against phage. The bacterial CARD is essential for protease-mediated activation of certain bacterial gasdermins, which promote cell death once phage infection is recognized. We further show that multiple anti-phage defense systems utilize CARD-like domains to activate a variety of cell death effectors. We find that these systems are triggered by a conserved immune evasion protein that phages use to overcome the bacterial defense system RexAB, demonstrating that phage proteins inhibiting one defense system can activate another. We also detect a phage protein with a predicted CARD-like structure that can inhibit the CARD-containing bacterial gasdermin system. Our results suggest that CARD domains represent an ancient component of innate immune systems conserved from bacteria to humans, and that CARD-dependent activation of gasdermins is conserved in organisms across the tree of life.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Membrane disrupting or other",
+ "PFAM": [
+ {
+ "ID": "Peptidase_S8",
+ "DE": "Subtilase family",
+ "GA": "21.8; 21.8;",
+ "TP": "Domain",
+ "ML": 283,
+ "CL": "",
+ "NE": "PD40",
+ "AC": "PF00082"
+ },
+ {
+ "ID": "Trypsin",
+ "DE": "Trypsin",
+ "GA": "20.6; 20.6;",
+ "TP": "Domain",
+ "ML": 220,
+ "CL": "CL0124",
+ "NE": "",
+ "AC": "PF00089"
+ },
+ {
+ "ID": "PLDc",
+ "DE": "Phospholipase D Active site motif",
+ "GA": "21.9; 21.9;",
+ "TP": "Family",
+ "ML": 28,
+ "CL": "CL0479",
+ "NE": "",
+ "AC": "PF00614"
+ },
+ {
+ "ID": "Endonuclease_NS",
+ "DE": "DNA/RNA non-specific endonuclease",
+ "GA": "23; 23;",
+ "TP": "Domain",
+ "ML": 223,
+ "CL": "CL0263",
+ "NE": "",
+ "AC": "PF01223"
+ },
+ {
+ "ID": "PLDc_2",
+ "DE": "PLD-like domain",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 132,
+ "CL": "CL0479",
+ "NE": "",
+ "AC": "PF13091"
+ },
+ {
+ "ID": "AAA_16",
+ "DE": "AAA ATPase domain",
+ "GA": "32.6; 32.6;",
+ "TP": "Domain",
+ "ML": 167,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13191"
+ },
+ {
+ "ID": "Trypsin_2",
+ "DE": "Trypsin-like peptidase domain",
+ "GA": "27.6; 27.6;",
+ "TP": "Domain",
+ "ML": 144,
+ "CL": "CL0124",
+ "NE": "",
+ "AC": "PF13365"
+ }
+ ]
+ },
+ {
+ "title": "AbiL",
+ "contributors": [
+ "Ernest Mordret"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1111/j.1574-6968.1997.tb10185.x"
+ },
+ {
+ "doi": "10.1016/j.mib.2005.06.006"
+ }
+ ],
+ "doi": "10.1111/j.1574-6968.1997.tb10185.x",
+ "abstract": "A 16-kb plasmid (pND859) was identified from Lactococcus lactis biovar. diacetylactis UK12922 which encodes phage resistance to the small isometric phage 712 when tested in L. lactis LM0230. The gene encoding phage abortive infection, designated abi-859, was localized on a 1.2-kb region which consists of an open reading frame (ORF) of 846 bp preceded by a potential ribosome-binding site and a putative promoter region. A helix-turn-helix region typical of DNA-binding motifs was identified near the N-terminal of the abi-859 product, suggesting a possible interaction with the phage DNA.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "AAA_15",
+ "DE": "AAA ATPase domain",
+ "GA": "32.1; 32.1;",
+ "TP": "Domain",
+ "ML": 399,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13175"
+ },
+ {
+ "ID": "AAA_21",
+ "DE": "AAA domain, putative AbiEii toxin, Type IV TA system",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 304,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13304"
+ },
+ {
+ "ID": "RloB",
+ "DE": "RloB-like protein",
+ "GA": "31.5; 31.5;",
+ "TP": "Domain",
+ "ML": 192,
+ "CL": "",
+ "NE": "",
+ "AC": "PF13707"
+ }
+ ]
+ },
+ {
+ "title": "Gao_Iet",
+ "doi": "10.1126/science.aba0372",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "AAA",
+ "DE": "ATPase family associated with various cellular activities (AAA)",
+ "GA": "21.2; 21.2;",
+ "TP": "Domain",
+ "ML": 131,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF00004"
+ },
+ {
+ "ID": "Peptidase_S8",
+ "DE": "Subtilase family",
+ "GA": "21.8; 21.8;",
+ "TP": "Domain",
+ "ML": 283,
+ "CL": "",
+ "NE": "PD40",
+ "AC": "PF00082"
+ }
+ ]
+ },
+ {
+ "title": "PD-T4-6",
+ "contributors": [
+ "Marian Dominguez-Mirazo"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1038/s41564-022-01219-4"
+ }
+ ],
+ "doi": "10.1038/s41564-022-01219-4",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "Pkinase",
+ "DE": "Protein kinase domain",
+ "GA": "31.7; 31.7;",
+ "TP": "Domain",
+ "ML": 263,
+ "CL": "CL0016",
+ "NE": "",
+ "AC": "PF00069"
+ },
+ {
+ "ID": "PASTA",
+ "DE": "PASTA domain",
+ "GA": "21.2; 21.2;",
+ "TP": "Domain",
+ "ML": 63,
+ "CL": "",
+ "NE": "",
+ "AC": "PF03793"
+ },
+ {
+ "ID": "PK_Tyr_Ser-Thr",
+ "DE": "Protein tyrosine and serine/threonine kinase",
+ "GA": "23.1; 23.1;",
+ "TP": "Domain",
+ "ML": 258,
+ "CL": "CL0016",
+ "NE": "",
+ "AC": "PF07714"
+ }
+ ]
+ },
+ {
+ "title": "Menshen",
+ "contributors": [
+ "Alba Herrero del Valle"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1016/j.chom.2022.09.017"
+ }
+ ],
+ "doi": "10.1016/j.chom.2022.09.017",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "DUF262",
+ "DE": "Protein of unknown function DUF262",
+ "GA": "33.2; 33.2;",
+ "TP": "Family",
+ "ML": 199,
+ "CL": "CL0248",
+ "NE": "",
+ "AC": "PF03235"
+ },
+ {
+ "ID": "Gp49",
+ "DE": "Phage derived protein Gp49-like (DUF891)",
+ "GA": "23.9; 23.9;",
+ "TP": "Domain",
+ "ML": 90,
+ "CL": "CL0136",
+ "NE": "",
+ "AC": "PF05973"
+ },
+ {
+ "ID": "DUF3696",
+ "DE": "Protein of unknown function (DUF3696)",
+ "GA": "22; 22;",
+ "TP": "Family",
+ "ML": 53,
+ "CL": "",
+ "NE": "",
+ "AC": "PF12476"
+ },
+ {
+ "ID": "AAA_15",
+ "DE": "AAA ATPase domain",
+ "GA": "32.1; 32.1;",
+ "TP": "Domain",
+ "ML": 399,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13175"
+ },
+ {
+ "ID": "AAA_21",
+ "DE": "AAA domain, putative AbiEii toxin, Type IV TA system",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 304,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13304"
+ },
+ {
+ "ID": "AAA_23",
+ "DE": "AAA domain",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 201,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13476"
+ }
+ ]
+ },
+ {
+ "title": "AbiG",
+ "doi": "10.1016/j.mib.2005.06.006",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "AbiGi",
+ "DE": "Putative abortive phage resistance protein AbiGi, antitoxin",
+ "GA": "22.4; 22.4;",
+ "TP": "Family",
+ "ML": 185,
+ "CL": "",
+ "NE": "",
+ "AC": "PF10899"
+ },
+ {
+ "ID": "AbiGii_2",
+ "DE": "Putative abortive phage resistance protein AbiGii toxin",
+ "GA": "25; 25;",
+ "TP": "Domain",
+ "ML": 397,
+ "CL": "",
+ "NE": "",
+ "AC": "PF16873"
+ }
+ ]
+ },
+ {
+ "title": "RexAB",
+ "doi": "10.1101/gad.6.3.497",
+ "abstract": "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.\n",
+ "Sensor": "Sensing of complex phage protein/DNA",
+ "Activator": "Direct",
+ "Effector": "Membrane disrupting",
+ "PFAM": [
+ {
+ "ID": "RexB",
+ "DE": "Membrane-anchored ion channel, Abi component",
+ "GA": "27; 27;",
+ "TP": "Family",
+ "ML": 139,
+ "CL": "",
+ "NE": "",
+ "AC": "PF15968"
+ },
+ {
+ "ID": "RexA",
+ "DE": "Intracellular sensor of Lambda phage, Abi component",
+ "GA": "25; 25;",
+ "TP": "Family",
+ "ML": 235,
+ "CL": "",
+ "NE": "",
+ "AC": "PF15969"
+ }
+ ]
+ },
+ {
+ "title": "AbiD",
+ "doi": "10.1016/j.mib.2005.06.006",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "Abi_2",
+ "DE": "Abi-like protein",
+ "GA": "25.6; 25.6;",
+ "TP": "Family",
+ "ML": 181,
+ "CL": "",
+ "NE": "",
+ "AC": "PF07751"
+ }
+ ]
+ },
+ {
+ "title": "PD-Lambda-5",
+ "contributors": [
+ "Nathalie Bechon"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1038/s41564-022-01219-4"
+ }
+ ],
+ "doi": "10.1038/s41564-022-01219-4",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "MethyltransfD12",
+ "DE": "D12 class N6 adenine-specific DNA methyltransferase",
+ "GA": "22; 22;",
+ "TP": "Family",
+ "ML": 253,
+ "CL": "CL0063",
+ "NE": "",
+ "AC": "PF02086"
+ }
+ ]
+ },
+ {
+ "title": "Dodola",
+ "contributors": [
+ "Ernest Mordret"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1016/j.chom.2022.09.017"
+ }
+ ],
+ "doi": "10.1016/j.chom.2022.09.017",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "AAA",
+ "DE": "ATPase family associated with various cellular activities (AAA)",
+ "GA": "21.2; 21.2;",
+ "TP": "Domain",
+ "ML": 131,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF00004"
+ },
+ {
+ "ID": "AAA_2",
+ "DE": "AAA domain (Cdc48 subfamily)",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 166,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF07724"
+ },
+ {
+ "ID": "AAA_5",
+ "DE": "AAA domain (dynein-related subfamily)",
+ "GA": "22; 22;",
+ "TP": "Domain",
+ "ML": 139,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF07728"
+ }
+ ]
+ },
+ {
+ "title": "Gao_Hhe",
+ "contributors": [
+ "Marian Dominguez-Mirazo"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1126/science.aba0372"
+ }
+ ],
+ "doi": "10.1126/science.aba0372",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "DUF559",
+ "DE": "Protein of unknown function (DUF559)",
+ "GA": "20.6; 20.6;",
+ "TP": "Family",
+ "ML": 109,
+ "CL": "CL0236",
+ "NE": "",
+ "AC": "PF04480"
+ },
+ {
+ "ID": "AAA_11",
+ "DE": "AAA domain",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 257,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13086"
+ },
+ {
+ "ID": "AAA_12",
+ "DE": "AAA domain",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 195,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13087"
+ },
+ {
+ "ID": "DUF4011",
+ "DE": "Protein of unknown function (DUF4011)",
+ "GA": "22.2; 22.2;",
+ "TP": "Family",
+ "ML": 158,
+ "CL": "",
+ "NE": "",
+ "AC": "PF13195"
+ },
+ {
+ "ID": "MTES_1575",
+ "DE": "REase_MTES_1575",
+ "GA": "38.2; 38.2;",
+ "TP": "Domain",
+ "ML": 96,
+ "CL": "CL0236",
+ "NE": "",
+ "AC": "PF18741"
+ }
+ ]
+ },
+ {
+ "title": "Zorya",
+ "doi": "10.1126/science.aar4120",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "SNF2-rel_dom",
+ "DE": "SNF2-related domain",
+ "GA": "23.9; 23.9;",
+ "TP": "Domain",
+ "ML": 290,
+ "CL": "CL0023",
+ "NE": "Bromodomain",
+ "AC": "PF00176"
+ },
+ {
+ "ID": "Helicase_C",
+ "DE": "Helicase conserved C-terminal domain",
+ "GA": "23.5; 23.5;",
+ "TP": "Domain",
+ "ML": 110,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF00271"
+ },
+ {
+ "ID": "OmpA",
+ "DE": "OmpA family",
+ "GA": "27.2; 27.2;",
+ "TP": "Family",
+ "ML": 98,
+ "CL": "",
+ "NE": "",
+ "AC": "PF00691"
+ },
+ {
+ "ID": "ResIII",
+ "DE": "Type III restriction enzyme, res subunit",
+ "GA": "22.5; 22.5;",
+ "TP": "Family",
+ "ML": 164,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF04851"
+ },
+ {
+ "ID": "EH_Signature",
+ "DE": "EH_Signature domain",
+ "GA": "27.5; 27.5;",
+ "TP": "Domain",
+ "ML": 424,
+ "CL": "",
+ "NE": "",
+ "AC": "PF15611"
+ }
+ ]
+ },
+ {
+ "title": "PD-T4-9",
+ "doi": "10.1038/s41564-022-01219-4",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "SecB",
+ "DE": "Preprotein translocase subunit SecB",
+ "GA": "26; 26;",
+ "TP": "Family",
+ "ML": 141,
+ "CL": "",
+ "NE": "",
+ "AC": "PF02556"
+ }
+ ]
+ },
+ {
+ "title": "RosmerTA",
+ "doi": "10.1016/j.chom.2022.09.017",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "HTH_3",
+ "DE": "Helix-turn-helix",
+ "GA": "23; 23;",
+ "TP": "Domain",
+ "ML": 55,
+ "CL": "CL0123",
+ "NE": "",
+ "AC": "PF01381"
+ },
+ {
+ "ID": "Peptidase_M78",
+ "DE": "IrrE N-terminal-like domain",
+ "GA": "22; 22;",
+ "TP": "Family",
+ "ML": 123,
+ "CL": "CL0126",
+ "NE": "",
+ "AC": "PF06114"
+ },
+ {
+ "ID": "HTH_19",
+ "DE": "Helix-turn-helix domain",
+ "GA": "30.2; 30.2;",
+ "TP": "Domain",
+ "ML": 64,
+ "CL": "CL0123",
+ "NE": "",
+ "AC": "PF12844"
+ },
+ {
+ "ID": "HTH_26",
+ "DE": "Cro/C1-type HTH DNA-binding domain",
+ "GA": "22; 22;",
+ "TP": "Domain",
+ "ML": 63,
+ "CL": "CL0123",
+ "NE": "",
+ "AC": "PF13443"
+ },
+ {
+ "ID": "HTH_31",
+ "DE": "Helix-turn-helix domain",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 64,
+ "CL": "CL0123",
+ "NE": "",
+ "AC": "PF13560"
+ }
+ ]
+ },
+ {
+ "title": "Rst_DUF4238",
+ "doi": "10.1016/j.chom.2022.02.018",
+ "abstract": "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.\u00a0coli 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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "DUF4238",
+ "DE": "Protein of unknown function (DUF4238)",
+ "GA": "27; 27;",
+ "TP": "Family",
+ "ML": 282,
+ "CL": "",
+ "NE": "",
+ "AC": "PF14022"
+ }
+ ]
+ },
+ {
+ "title": "Rst_TIR-NLR",
+ "doi": "10.1016/j.chom.2022.02.018",
+ "abstract": "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.\u00a0coli 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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "TIR_2",
+ "DE": "TIR domain",
+ "GA": "28; 28;",
+ "TP": "Domain",
+ "ML": 122,
+ "CL": "CL0173",
+ "NE": "",
+ "AC": "PF13676"
+ }
+ ]
+ },
+ {
+ "title": "Hna",
+ "doi": "10.1016/j.chom.2023.01.010",
+ "abstract": "There is strong selection for the evolution of systems that protect bacterial populations from viral attack. We report a single phage defense protein, Hna, that provides protection against diverse phages in Sinorhizobium meliloti, a nitrogen-fixing alpha-proteobacterium. Homologs of Hna are distributed widely across bacterial lineages, and a homologous protein from Escherichia coli also confers phage defense. Hna contains superfamily II helicase motifs at its N terminus and a nuclease motif at its C terminus, with mutagenesis of these motifs inactivating viral defense. Hna variably impacts phage DNA replication but consistently triggers an abortive infection response in which infected cells carrying the system die but do not release phage progeny. A similar host cell response is triggered in cells containing Hna upon expression of a phage-encoded single-stranded DNA binding protein (SSB), independent of phage infection. Thus, we conclude that Hna limits phage spread by initiating abortive infection in response to a phage protein.\n",
+ "PFAM": [
+ {
+ "ID": "DEAD",
+ "DE": "DEAD/DEAH box helicase",
+ "GA": "26; 24.1;",
+ "TP": "Domain",
+ "ML": 166,
+ "CL": "CL0023",
+ "NE": "SPRY",
+ "AC": "PF00270"
+ },
+ {
+ "ID": "ResIII",
+ "DE": "Type III restriction enzyme, res subunit",
+ "GA": "22.5; 22.5;",
+ "TP": "Family",
+ "ML": 164,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF04851"
+ },
+ {
+ "ID": "Helicase_C_2",
+ "DE": "Helicase C-terminal domain",
+ "GA": "25.3; 25.3;",
+ "TP": "Domain",
+ "ML": 170,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13307"
+ }
+ ]
+ },
+ {
+ "title": "PD-T4-10",
+ "contributors": [
+ "Alba Herrero del Valle"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1038/s41564-022-01219-4"
+ }
+ ],
+ "doi": "10.1038/s41564-022-01219-4",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": []
+ },
+ {
+ "title": "PD-T4-5",
+ "doi": "10.1038/s41564-022-01219-4",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "Abi_2",
+ "DE": "Abi-like protein",
+ "GA": "25.6; 25.6;",
+ "TP": "Family",
+ "ML": 181,
+ "CL": "",
+ "NE": "",
+ "AC": "PF07751"
+ }
+ ]
+ },
+ {
+ "title": "Eleos",
+ "doi": "10.1016/j.chom.2022.09.017",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "Dynamin_N",
+ "DE": "Dynamin family",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 168,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF00350"
+ },
+ {
+ "ID": "MMR_HSR1",
+ "DE": "50S ribosome-binding GTPase",
+ "GA": "21.9; 21.9;",
+ "TP": "Family",
+ "ML": 113,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF01926"
+ },
+ {
+ "ID": "DLP_helical",
+ "DE": "Dynamin-like helical domain",
+ "GA": "25.5; 25.5;",
+ "TP": "Domain",
+ "ML": 340,
+ "CL": "",
+ "NE": "",
+ "AC": "PF18709"
+ }
+ ]
+ },
+ {
+ "title": "CBASS",
+ "doi": "10.1038/s41564-020-0777-y",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Signaling molecules",
+ "Effector": "Divers (Nucleic acid degrading, Nucleotide modifying, Membrane disrupting)",
+ "PFAM": [
+ {
+ "ID": "AAA",
+ "DE": "ATPase family associated with various cellular activities (AAA)",
+ "GA": "21.2; 21.2;",
+ "TP": "Domain",
+ "ML": 131,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF00004"
+ },
+ {
+ "ID": "cNMP_binding",
+ "DE": "Cyclic nucleotide-binding domain",
+ "GA": "27.5; 27.5;",
+ "TP": "Domain",
+ "ML": 89,
+ "CL": "CL0029",
+ "NE": "",
+ "AC": "PF00027"
+ },
+ {
+ "ID": "ThiF",
+ "DE": "ThiF family",
+ "GA": "28.1; 28.1;",
+ "TP": "Domain",
+ "ML": 219,
+ "CL": "CL0063",
+ "NE": "UBA_E1_SCCH",
+ "AC": "PF00899"
+ },
+ {
+ "ID": "PNP_UDP_1",
+ "DE": "Phosphorylase superfamily",
+ "GA": "25.1; 25.1;",
+ "TP": "Domain",
+ "ML": 233,
+ "CL": "CL0408",
+ "NE": "",
+ "AC": "PF01048"
+ },
+ {
+ "ID": "Patatin",
+ "DE": "Patatin-like phospholipase",
+ "GA": "27.7; 27.7;",
+ "TP": "Family",
+ "ML": 191,
+ "CL": "CL0323",
+ "NE": "",
+ "AC": "PF01734"
+ },
+ {
+ "ID": "QueC",
+ "DE": "Queuosine biosynthesis protein QueC",
+ "GA": "22; 22;",
+ "TP": "Domain",
+ "ML": 210,
+ "CL": "CL0039",
+ "NE": "",
+ "AC": "PF06508"
+ },
+ {
+ "ID": "CAP12-PCTIR_TIR",
+ "DE": "CAP12/Pycsar effector protein, TIR domain",
+ "GA": "24.7; 24.7;",
+ "TP": "Domain",
+ "ML": 119,
+ "CL": "CL0173",
+ "NE": "",
+ "AC": "PF10137"
+ },
+ {
+ "ID": "Prok-E2_B",
+ "DE": "Prokaryotic E2 family B",
+ "GA": "25.4; 25.4;",
+ "TP": "Family",
+ "ML": 135,
+ "CL": "CL0208",
+ "NE": "",
+ "AC": "PF14461"
+ },
+ {
+ "ID": "Prok-JAB",
+ "DE": "Prokaryotic homologs of the JAB domain",
+ "GA": "25; 25;",
+ "TP": "Family",
+ "ML": 114,
+ "CL": "CL0366",
+ "NE": "",
+ "AC": "PF14464"
+ },
+ {
+ "ID": "AGS_C",
+ "DE": "Adenylyl/Guanylyl and SMODS C-terminal sensor domain",
+ "GA": "26.7; 26.7;",
+ "TP": "Domain",
+ "ML": 129,
+ "CL": "",
+ "NE": "",
+ "AC": "PF18134"
+ },
+ {
+ "ID": "bacHORMA_1",
+ "DE": "Bacterial HORMA domain family 1",
+ "GA": "35.6; 35.6;",
+ "TP": "Domain",
+ "ML": 169,
+ "CL": "",
+ "NE": "",
+ "AC": "PF18138"
+ },
+ {
+ "ID": "SMODS",
+ "DE": "Second Messenger Oligonucleotide or Dinucleotide Synthetase domain",
+ "GA": "26.5; 30;",
+ "TP": "Domain",
+ "ML": 164,
+ "CL": "CL0260",
+ "NE": "",
+ "AC": "PF18144"
+ },
+ {
+ "ID": "SAVED",
+ "DE": "SMODS-associated and fused to various effectors sensor domain",
+ "GA": "26.2; 26.2;",
+ "TP": "Domain",
+ "ML": 189,
+ "CL": "",
+ "NE": "",
+ "AC": "PF18145"
+ },
+ {
+ "ID": "S_2TMBeta",
+ "DE": "SMODS-associating 2TM, beta-strand rich effector domain",
+ "GA": "31.2; 31.2;",
+ "TP": "Domain",
+ "ML": 181,
+ "CL": "",
+ "NE": "",
+ "AC": "PF18153"
+ },
+ {
+ "ID": "S_4TM",
+ "DE": "SMODS-associating 4TM effector domain",
+ "GA": "26.9; 26.9;",
+ "TP": "Domain",
+ "ML": 290,
+ "CL": "CL0676",
+ "NE": "",
+ "AC": "PF18159"
+ },
+ {
+ "ID": "Sa_NUDIX",
+ "DE": "SMODS-associated NUDIX domain",
+ "GA": "25; 25;",
+ "TP": "Domain",
+ "ML": 199,
+ "CL": "",
+ "NE": "",
+ "AC": "PF18167"
+ },
+ {
+ "ID": "bacHORMA_2",
+ "DE": "Bacterial HORMA domain 2",
+ "GA": "27.3; 27.3;",
+ "TP": "Domain",
+ "ML": 166,
+ "CL": "CL0651",
+ "NE": "",
+ "AC": "PF18173"
+ },
+ {
+ "ID": "TPALS",
+ "DE": "TIR- and PNP-associating SLOG family",
+ "GA": "26.6; 26.6;",
+ "TP": "Family",
+ "ML": 232,
+ "CL": "CL0349",
+ "NE": "",
+ "AC": "PF18178"
+ },
+ {
+ "ID": "SUa-2TM",
+ "DE": "SMODS- and Ubiquitin system-associated 2TM effector domain",
+ "GA": "25; 25;",
+ "TP": "Domain",
+ "ML": 279,
+ "CL": "",
+ "NE": "",
+ "AC": "PF18179"
+ },
+ {
+ "ID": "SLATT_4",
+ "DE": "SMODS and SLOG-associating 2TM effector domain family 4",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 165,
+ "CL": "CL0676",
+ "NE": "",
+ "AC": "PF18186"
+ },
+ {
+ "ID": "Saf_2TM",
+ "DE": "SAVED-fused 2TM effector domain",
+ "GA": "29.5; 29.5;",
+ "TP": "Domain",
+ "ML": 152,
+ "CL": "",
+ "NE": "",
+ "AC": "PF18303"
+ },
+ {
+ "ID": "PycTM",
+ "DE": "Pycsar effector protein",
+ "GA": "27.2; 27.2;",
+ "TP": "Family",
+ "ML": 107,
+ "CL": "",
+ "NE": "",
+ "AC": "PF18967"
+ }
+ ]
+ },
+ {
+ "title": "DarTG",
+ "contributors": [
+ "Ernest Mordret"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1038/s41564-022-01153-5"
+ },
+ {
+ "doi": "10.1016/j.molcel.2016.11.014"
+ },
+ {
+ "doi": "10.1016/j.celrep.2020.01.014"
+ },
+ {
+ "doi": "10.1038/s41586-021-03825-4"
+ }
+ ],
+ "doi": "10.1038/s41564-022-01153-5",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Direct binding to ssDNA",
+ "Effector": "Nucleic acid degrading (ADP-ribosylation)",
+ "PFAM": [
+ {
+ "ID": "Macro",
+ "DE": "Macro domain",
+ "GA": "22; 22;",
+ "TP": "Domain",
+ "ML": 118,
+ "CL": "CL0223",
+ "NE": "",
+ "AC": "PF01661"
+ },
+ {
+ "ID": "DarT",
+ "DE": "ssDNA thymidine ADP-ribosyltransferase, DarT",
+ "GA": "22.5; 22.5;",
+ "TP": "Family",
+ "ML": 200,
+ "CL": "CL0084",
+ "NE": "",
+ "AC": "PF14487"
+ }
+ ]
+ },
+ {
+ "title": "Kiwa",
+ "contributors": [
+ "Lucas Paoli"
+ ],
+ "relevantAbstracts": [
+ {
+ "doi": "10.1126/science.aar4120"
+ },
+ {
+ "doi": "10.1101/2023.02.26.530102"
+ }
+ ],
+ "doi": "10.1126/science.aar4120",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "KwaB",
+ "DE": "Kiwa protein KwaB-like",
+ "GA": "26.3; 26.3;",
+ "TP": "Family",
+ "ML": 187,
+ "CL": "",
+ "NE": "",
+ "AC": "PF16162"
+ }
+ ]
+ },
+ {
+ "title": "Wadjet",
+ "doi": "10.1126/science.aar4120",
+ "abstract": "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.\n",
+ "Sensor": "Detecting invading nucleic acid",
+ "Activator": "Direct",
+ "Effector": "Nucleic acid degrading",
+ "PFAM": [
+ {
+ "ID": "DUF2397",
+ "DE": "Protein of unknown function (DUF2397)",
+ "GA": "28.5; 28.5;",
+ "TP": "Family",
+ "ML": 483,
+ "CL": "",
+ "NE": "",
+ "AC": "PF09660"
+ },
+ {
+ "ID": "DUF2398",
+ "DE": "Protein of unknown function (DUF2398)",
+ "GA": "26.9; 26.9;",
+ "TP": "Family",
+ "ML": 360,
+ "CL": "",
+ "NE": "",
+ "AC": "PF09661"
+ },
+ {
+ "ID": "DUF2399",
+ "DE": "Protein of unknown function C-terminus (DUF2399)",
+ "GA": "23.4; 23.4;",
+ "TP": "Domain",
+ "ML": 152,
+ "CL": "CL0413",
+ "NE": "",
+ "AC": "PF09664"
+ },
+ {
+ "ID": "JetD_C",
+ "DE": "Wadjet protein JetD, C-terminal",
+ "GA": "22; 22;",
+ "TP": "Domain",
+ "ML": 181,
+ "CL": "CL0413",
+ "NE": "",
+ "AC": "PF09983"
+ },
+ {
+ "ID": "DUF3322",
+ "DE": "Uncharacterized protein conserved in bacteria N-term (DUF3322)",
+ "GA": "22; 22;",
+ "TP": "Domain",
+ "ML": 190,
+ "CL": "",
+ "NE": "",
+ "AC": "PF11795"
+ },
+ {
+ "ID": "DUF3323",
+ "DE": "Protein of unknown function N-terminus (DUF3323)",
+ "GA": "26.6; 26.6;",
+ "TP": "Family",
+ "ML": 209,
+ "CL": "",
+ "NE": "",
+ "AC": "PF11796"
+ },
+ {
+ "ID": "DUF3375",
+ "DE": "Protein of unknown function (DUF3375)",
+ "GA": "28.6; 28.6;",
+ "TP": "Family",
+ "ML": 474,
+ "CL": "",
+ "NE": "",
+ "AC": "PF11855"
+ },
+ {
+ "ID": "AAA_29",
+ "DE": "P-loop containing region of AAA domain",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 61,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13555"
+ },
+ {
+ "ID": "SbcC_Walker_B",
+ "DE": "SbcC/RAD50-like, Walker B motif",
+ "GA": "27; 27;",
+ "TP": "Domain",
+ "ML": 90,
+ "CL": "CL0023",
+ "NE": "",
+ "AC": "PF13558"
+ },
+ {
+ "ID": "DUF4194",
+ "DE": "Domain of unknown function (DUF4194)",
+ "GA": "32.7; 32.7;",
+ "TP": "Family",
+ "ML": 165,
+ "CL": "CL0123",
+ "NE": "",
+ "AC": "PF13835"
+ }
+ ]
+ },
+ {
+ "title": "PfiAT",
+ "doi": "10.1111/1751-7915.13570",
+ "abstract": "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.\n",
+ "Sensor": "Unknown",
+ "Activator": "Unknown",
+ "Effector": "Unknown",
+ "PFAM": [
+ {
+ "ID": "PhdYeFM_antitox",
+ "DE": "Antitoxin Phd_YefM, type II toxin-antitoxin system",
+ "GA": "29.8; 29.8;",
+ "TP": "Domain",
+ "ML": 74,
+ "CL": "CL0136",
+ "NE": "",
+ "AC": "PF02604"
+ },
+ {
+ "ID": "ParE_toxin",
+ "DE": "ParE toxin of type II toxin-antitoxin system, parDE",
+ "GA": "23; 23;",
+ "TP": "Domain",
+ "ML": 89,
+ "CL": "CL0136",
+ "NE": "",
+ "AC": "PF05016"
+ }
+ ]
+ }
]
\ No newline at end of file