identifier: traitmech:000461 label: DS-39 system definition: A phage defense system in which an organism possesses the single-gene DefensePredictor-discovered system 39 locus cataloged as working transcriptional unit AAA5 and whose plasmid expression in E. coli MG1655 reduced bacteriophage plaquing. definition_source: DOI:10.1126/science.adv7924 trait_category: GENOMICS term_kind: CLASS mapping_status: PROPOSED parent_traits: - traitmech:000209 synonyms: - synonym_text: DS-39 synonym_type: EXACT_SYNONYM source: DOI:10.1126/science.adv7924 - synonym_text: AAA5 synonym_type: RELATED_SYNONYM source: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx - synonym_text: DS-39__DS-39 synonym_type: RELATED_SYNONYM source: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md evidence: - reference: DOI:10.1126/science.adv7924 snippet: To test for anti-phage defense, we placed each TU with its predicted native promoter region on a low-copy number plasmid in E. coli MG1655 and challenged these strains with a panel of 24 diverse E. coli phages (Fig. 3; fig. S2). In total, 42 (45% of 94) of the cloned TUs produced smaller plaque sizes or reduced the efficiency of plating (EOP) at least ten-fold relative to an empty vector control strain notes: DeWeirdt et al. experimentally validated 42 predicted transcriptional units as phage-defense systems in E. coli. - reference: DOI:10.1126/science.adv7924 snippet: We refer to these validated TUs as DefensePredictor discovered systems (DSs), with genes in multi-gene TUs denoted by an alphabetical suffix, e.g., DS-8A is the first gene of DS-8. notes: DeWeirdt et al. name validated transcriptional units as DefensePredictor discovered systems. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx snippet: "AAA5\tNZ_RRWS01000024.1\tGCF_003892555.1\t+\tTrue\tFalse\tTrue\tTrue\t\ DefensePredictor hits\t12586\t14718\tMarR family transcriptional regulator\tWP_042346724.1\t\ 9.53722790980957\t3.842009204807092\tTrue\tTrue\tPredicted novel defense gene\t\ DS-39" notes: The final Science supplementary Table S6 maps working_id AAA5 to DS_name DS-39, marks the cloned transcriptional unit as defensive, and records NZ_RRWS01000024.1 positions 12586-14718 with product accession WP_042346724.1. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx snippet: "Bas1\t3.1\tpLAND\t24-04-10_CITO_AAA3_FDRT_EV.png\t5000000\tAAA5\t24-04-10\t\ 24-04-10_HTHO_AAA5.png\t0\t1\t\t1\t6.698970004336019\t\tTrue\t\tLB\t37" notes: The final Science supplementary Table S7 Systems sheet reports an AAA5 assay row with a Bas1 phage readout and a -log(EOP) value of 6.699. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx snippet: "Bas3\t3.1\tpLAND\t24-04-10_CITO_AAA3_FDRT_EV.png\t200000000\tAAA5\t24-04-10\t\ 24-04-10_HTHO_AAA5.png\t3\t7\tY\t7000\t4.455931955649724\t\tTrue\t\tLB\t37" notes: The final Science supplementary Table S7 Systems sheet reports an AAA5 assay row with a Bas3 phage readout and a -log(EOP) value of 4.456. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx snippet: "AAA5\tDS-39\tTrue" notes: The final Science supplementary Table S8 maps AAA5 to replicated display name DS-39. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx snippet: "AAA5\t1.0\t710.0\tWP_042346724.1\tAAA+ ATPase\t7MCA_I\tCell division control\ \ protein 6; replication initiation, REPLICATION\thhpred_6053627.hhr\t53.0\t540.0\t\ 0.9852\t2024-04-15 00:00:00\t\t" notes: The final Science supplementary Table S8 reports a high-probability AAA+ ATPase HHpred hit for WP_042346724.1 in AAA5. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx snippet: "AAA5\t1.0\t710.0\tWP_042346724.1\tZF\tPF18256.5\tHscB_4_cys ; Co-chaperone\ \ HscB tetracysteine metal binding motif\thhpred_6053627.hhr\t583.0\t615.0\t0.87\t\ 2024-04-15 00:00:00\t\t" notes: The final Science supplementary Table S8 reports a moderate-probability zinc-finger HHpred hit for WP_042346724.1 in AAA5. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx snippet: "AAA5\t1.0\t710.0\tWP_042346724.1\tHTH\t5HS5_B\tHTH-type transcriptional\ \ regulator SarX\thhpred_6053627.hhr\t623.0\t706.0\t0.98\t2024-04-15 00:00:00\t\ \t" notes: The final Science supplementary Table S8 reports a high-probability HTH HHpred hit for WP_042346724.1 in AAA5. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md snippet: '| DS-39 | 10\.1101/2025\.01\.08\.631726 | DefensePredictor: A machine learning model to discover novel prokaryotic immune systems | ' notes: The pinned DefenseFinder article registry maps the DS-39 source key to the preprint DOI for the DeWeirdt et al. DefensePredictor study, which has since been published in Science. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md snippet: '| DS-39__DS-39 | | DS-39 | Custom | 200 |' notes: The pinned DefenseFinder HMM inventory records DS-39__DS-39 as a custom DS-39 profile. causal_graphs: - graph_id: ds_39_locus_reduces_phage_plaquing title: DS-39 locus reduces bacteriophage plaquing description: Conservative system-level sketch linking the single-gene DS-39 locus to reduced bacteriophage plaquing without resolving DS-39 component function or molecular output. scope_status: NONMECHANISTIC scope_notes: The graph captures DS-39 as the validated AAA5 transcriptional unit with one product accession, high-probability AAA+ ATPase and HTH HHpred rows for WP_042346724.1, a moderate-probability zinc-finger HHpred row for WP_042346724.1, and one DefenseFinder DS-39 profile row. It does not assert exact profile-to-protein correspondence, AAA+ ATPase activity, HTH DNA-binding activity, zinc-finger metal-binding activity, native host breadth, DS-39 molecular output, complete phage breadth, or DefenseFinder rule-level detection criteria. nodes: - node_id: ds_39_locus label: DS-39 locus node_type: GENETIC_ELEMENT description: A single-gene DefensePredictor-discovered system 39 locus represented in the pinned DefenseFinder HMM inventory by one DS-39 custom profile. - node_id: reduced_phage_plaquing label: reduced bacteriophage plaquing node_type: BIOLOGICAL_PROCESS description: Reduced bacteriophage plaquing in cells carrying cloned AAA5. - node_id: ds_39_system_trait label: DS-39 system node_type: TRAIT grounding: traitmech:000461 description: Possession of a genome-encoded DS-39 phage-defense system. - node_id: phage_defense_system label: phage defense system node_type: TRAIT grounding: traitmech:000209 description: Possession of one or more genome-encoded immune systems that inhibit bacteriophage infection. edges: - subject: ds_39_locus predicate: contributes to predicate_id: RO:0002326 object: reduced_phage_plaquing description: The DS-39/AAA5 locus contributes to reduced bacteriophage plaquing in heterologous E. coli MG1655 plasmid-expression assays. evidence: - reference: DOI:10.1126/science.adv7924 snippet: To test for anti-phage defense, we placed each TU with its predicted native promoter region on a low-copy number plasmid in E. coli MG1655 and challenged these strains with a panel of 24 diverse E. coli phages (Fig. 3; fig. S2). In total, 42 (45% of 94) of the cloned TUs produced smaller plaque sizes or reduced the efficiency of plating (EOP) at least ten-fold relative to an empty vector control strain notes: DeWeirdt et al. describe the plasmid-based phage challenge used to validate predicted transcriptional units. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx snippet: "AAA5\tNZ_RRWS01000024.1\tGCF_003892555.1\t+\tTrue\tFalse\tTrue\tTrue\t\ DefensePredictor hits\t12586\t14718\tMarR family transcriptional regulator\t\ WP_042346724.1\t9.53722790980957\t3.842009204807092\tTrue\tTrue\tPredicted\ \ novel defense gene\tDS-39" notes: The final Science supplementary Table S6 maps working_id AAA5 to DS_name DS-39, marks the cloned transcriptional unit as defensive, and records NZ_RRWS01000024.1 positions 12586-14718 with product accession WP_042346724.1. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx snippet: "Bas1\t3.1\tpLAND\t24-04-10_CITO_AAA3_FDRT_EV.png\t5000000\tAAA5\t\ 24-04-10\t24-04-10_HTHO_AAA5.png\t0\t1\t\t1\t6.698970004336019\t\tTrue\t\t\ LB\t37" notes: The final Science supplementary Table S7 Systems sheet reports an AAA5 assay row with a Bas1 phage readout and a -log(EOP) value of 6.699. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx snippet: "Bas3\t3.1\tpLAND\t24-04-10_CITO_AAA3_FDRT_EV.png\t200000000\tAAA5\t\ 24-04-10\t24-04-10_HTHO_AAA5.png\t3\t7\tY\t7000\t4.455931955649724\t\tTrue\t\ \tLB\t37" notes: The final Science supplementary Table S7 Systems sheet reports an AAA5 assay row with a Bas3 phage readout and a -log(EOP) value of 4.456. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx snippet: "AAA5\tDS-39\tTrue" notes: The final Science supplementary Table S8 maps AAA5 to replicated display name DS-39. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx snippet: "AAA5\t1.0\t710.0\tWP_042346724.1\tAAA+ ATPase\t7MCA_I\tCell division\ \ control protein 6; replication initiation, REPLICATION\thhpred_6053627.hhr\t\ 53.0\t540.0\t0.9852\t2024-04-15 00:00:00\t\t" notes: The final Science supplementary Table S8 reports a high-probability AAA+ ATPase HHpred hit for WP_042346724.1 in AAA5. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx snippet: "AAA5\t1.0\t710.0\tWP_042346724.1\tZF\tPF18256.5\tHscB_4_cys ; Co-chaperone\ \ HscB tetracysteine metal binding motif\thhpred_6053627.hhr\t583.0\t615.0\t\ 0.87\t2024-04-15 00:00:00\t\t" notes: The final Science supplementary Table S8 reports a moderate-probability zinc-finger HHpred hit for WP_042346724.1 in AAA5. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx snippet: "AAA5\t1.0\t710.0\tWP_042346724.1\tHTH\t5HS5_B\tHTH-type transcriptional\ \ regulator SarX\thhpred_6053627.hhr\t623.0\t706.0\t0.98\t2024-04-15 00:00:00\t\ \t" notes: The final Science supplementary Table S8 reports a high-probability HTH HHpred hit for WP_042346724.1 in AAA5. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md snippet: '| DS-39__DS-39 | | DS-39 | Custom | 200 |' notes: The pinned DefenseFinder HMM inventory records DS-39__DS-39 as a custom DS-39 profile. - subject: reduced_phage_plaquing predicate: confers predicate_id: METPO:2007700 object: ds_39_system_trait description: DS-39-mediated phage plaquing reduction realizes the DS-39 system trait. evidence: - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx snippet: "AAA5\tNZ_RRWS01000024.1\tGCF_003892555.1\t+\tTrue\tFalse\tTrue\tTrue\t\ DefensePredictor hits\t12586\t14718\tMarR family transcriptional regulator\t\ WP_042346724.1\t9.53722790980957\t3.842009204807092\tTrue\tTrue\tPredicted\ \ novel defense gene\tDS-39" notes: The final Science supplementary Table S6 maps working_id AAA5 to DS_name DS-39, marks the cloned transcriptional unit as defensive, and records NZ_RRWS01000024.1 positions 12586-14718 with product accession WP_042346724.1. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx snippet: "Bas1\t3.1\tpLAND\t24-04-10_CITO_AAA3_FDRT_EV.png\t5000000\tAAA5\t\ 24-04-10\t24-04-10_HTHO_AAA5.png\t0\t1\t\t1\t6.698970004336019\t\tTrue\t\t\ LB\t37" notes: The final Science supplementary Table S7 Systems sheet reports an AAA5 assay row with a Bas1 phage readout and a -log(EOP) value of 6.699. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx snippet: "Bas3\t3.1\tpLAND\t24-04-10_CITO_AAA3_FDRT_EV.png\t200000000\tAAA5\t\ 24-04-10\t24-04-10_HTHO_AAA5.png\t3\t7\tY\t7000\t4.455931955649724\t\tTrue\t\ \tLB\t37" notes: The final Science supplementary Table S7 Systems sheet reports an AAA5 assay row with a Bas3 phage readout and a -log(EOP) value of 4.456. - reference: DOI:10.1126/science.adv7924 snippet: We refer to these validated TUs as DefensePredictor discovered systems (DSs), with genes in multi-gene TUs denoted by an alphabetical suffix, e.g., DS-8A is the first gene of DS-8. notes: The DS nomenclature is used for DefensePredictor discovered systems. - subject: ds_39_system_trait predicate: is a predicate_id: rdfs:subClassOf object: phage_defense_system description: DS-39 system possession is a phage-defense-system trait. evidence: - reference: DOI:10.1126/science.adv7924 snippet: We refer to these validated TUs as DefensePredictor discovered systems (DSs), with genes in multi-gene TUs denoted by an alphabetical suffix, e.g., DS-8A is the first gene of DS-8. notes: DeWeirdt et al. name validated TUs as DefensePredictor discovered systems. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md snippet: '| DS-39 | 10\.1101/2025\.01\.08\.631726 | DefensePredictor: A machine learning model to discover novel prokaryotic immune systems | ' notes: The pinned DefenseFinder article registry maps the DS-39 source key to the preprint DOI for the DeWeirdt et al. DefensePredictor study, which has since been published in Science. discussions: - discussion_id: ds-39-defensefinder-model-gap prompt: Resolve DS-39 native host breadth, exact component activity, profile-to-protein mapping, AAA+ ATPase interpretation, HTH/zinc-finger interpretation, complete phage breadth, molecular output, and rule-level DefenseFinder criteria before minting narrower DS-39 mechanism children. kind: KNOWLEDGE_GAP status: OPEN rationale: DeWeirdt et al. support DS-39 as the defensive AAA5 transcriptional unit and final Science Tables S6/S7/S8 map it to one product accession, Bas1 and Bas3 phage readouts, display name DS-39, high-probability AAA+ ATPase and HTH HHpred rows, and a moderate-probability zinc-finger HHpred row. The pinned DefenseFinder HMM inventory records one DS-39 custom profile row. The pinned rules table has no DS-39 row, and the first-pass record does not resolve native host breadth, complete phage breadth, direct profile-to-protein correspondence, AAA+ ATPase activity, HTH or zinc-finger interpretation, molecular output, or endogenous DS-39 activity. evidence: - reference: DOI:10.1126/science.adv7924 snippet: We refer to these validated TUs as DefensePredictor discovered systems (DSs), with genes in multi-gene TUs denoted by an alphabetical suffix, e.g., DS-8A is the first gene of DS-8. notes: DeWeirdt et al. name validated TUs as DSs. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx snippet: "AAA5\tNZ_RRWS01000024.1\tGCF_003892555.1\t+\tTrue\tFalse\tTrue\tTrue\t\ DefensePredictor hits\t12586\t14718\tMarR family transcriptional regulator\t\ WP_042346724.1\t9.53722790980957\t3.842009204807092\tTrue\tTrue\tPredicted novel\ \ defense gene\tDS-39" notes: The final Science supplementary Table S6 maps working_id AAA5 to DS_name DS-39, marks the cloned transcriptional unit as defensive, and records NZ_RRWS01000024.1 positions 12586-14718 with product accession WP_042346724.1. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx snippet: "Bas1\t3.1\tpLAND\t24-04-10_CITO_AAA3_FDRT_EV.png\t5000000\tAAA5\t24-04-10\t\ 24-04-10_HTHO_AAA5.png\t0\t1\t\t1\t6.698970004336019\t\tTrue\t\tLB\t37" notes: The final Science supplementary Table S7 Systems sheet reports an AAA5 assay row with a Bas1 phage readout and a -log(EOP) value of 6.699. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx snippet: "Bas3\t3.1\tpLAND\t24-04-10_CITO_AAA3_FDRT_EV.png\t200000000\tAAA5\t\ 24-04-10\t24-04-10_HTHO_AAA5.png\t3\t7\tY\t7000\t4.455931955649724\t\tTrue\t\ \tLB\t37" notes: The final Science supplementary Table S7 Systems sheet reports an AAA5 assay row with a Bas3 phage readout and a -log(EOP) value of 4.456. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx snippet: "AAA5\tDS-39\tTrue" notes: The final Science supplementary Table S8 maps AAA5 to replicated display name DS-39. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx snippet: "AAA5\t1.0\t710.0\tWP_042346724.1\tAAA+ ATPase\t7MCA_I\tCell division\ \ control protein 6; replication initiation, REPLICATION\thhpred_6053627.hhr\t\ 53.0\t540.0\t0.9852\t2024-04-15 00:00:00\t\t" notes: The final Science supplementary Table S8 reports a high-probability AAA+ ATPase HHpred hit for WP_042346724.1 in AAA5. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx snippet: "AAA5\t1.0\t710.0\tWP_042346724.1\tZF\tPF18256.5\tHscB_4_cys ; Co-chaperone\ \ HscB tetracysteine metal binding motif\thhpred_6053627.hhr\t583.0\t615.0\t\ 0.87\t2024-04-15 00:00:00\t\t" notes: The final Science supplementary Table S8 reports a moderate-probability zinc-finger HHpred hit for WP_042346724.1 in AAA5. - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx snippet: "AAA5\t1.0\t710.0\tWP_042346724.1\tHTH\t5HS5_B\tHTH-type transcriptional\ \ regulator SarX\thhpred_6053627.hhr\t623.0\t706.0\t0.98\t2024-04-15 00:00:00\t\ \t" notes: The final Science supplementary Table S8 reports a high-probability HTH HHpred hit for WP_042346724.1 in AAA5. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md snippet: '| DS-39 | 10\.1101/2025\.01\.08\.631726 | DefensePredictor: A machine learning model to discover novel prokaryotic immune systems | ' notes: The pinned DefenseFinder article registry maps the DS-39 source key to the preprint DOI for the DeWeirdt et al. DefensePredictor study, which has since been published in Science. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md snippet: '| DS-39__DS-39 | | DS-39 | Custom | 200 |' notes: The pinned DefenseFinder HMM inventory records DS-39__DS-39 as a custom DS-39 profile. - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv notes: The pinned DefenseFinder rules table does not list DS-39, leaving rule-level detection criteria unresolved. attaches_to: - causal_graphs#ds_39_locus_reduces_phage_plaquing posed_by: codex posed_date: '2026-09-29' curation_history: - timestamp: '2026-09-29T11:35:06Z' curator: codex action: MINTED_TRAITMECH_ID changes: Minted DS-39 system as a DOI-backed GENOMICS TraitRecord under phage defense system after an ignored-and-hidden duplicate review found no exact live TraitMech, METPO, history, or prior proposal record; kept the graph at AAA5 transcriptional-unit level because the AAA+ ATPase, HTH, zinc-finger, and rule rows remain unresolved, and proposals/metpo_traitmech_v338 reserves the replacement placeholder. llm_assisted: true - timestamp: '2026-09-29T11:35:07Z' curator: codex action: REVIEW_CANONICAL_EXAMPLE_EVIDENCE_GAP changes: Reviewed DS-39 system canonical_examples and left them empty because DeWeirdt et al. directly support cloned AAA5 assays in E. coli MG1655 and a DefenseFinder DS-39 model, but not a direct named native microbial isolate exemplar with experimentally verified endogenous DS-39 activity. No paid research was used. llm_assisted: true