DS-39 system

traitmech:000461 · CLASS · PROPOSED

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.

Trait evidence (11)

DOI:10.1126/science.adv7924
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

DeWeirdt et al. experimentally validated 42 predicted transcriptional units as phage-defense systems in E. coli.
DOI:10.1126/science.adv7924
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.

DeWeirdt et al. name validated transcriptional units as DefensePredictor discovered systems.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
AAA5 NZ_RRWS01000024.1 GCF_003892555.1 + True False True True DefensePredictor hits 12586 14718 MarR family transcriptional regulator WP_042346724.1 9.53722790980957 3.842009204807092 True True Predicted novel defense gene DS-39

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.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
Bas1 3.1 pLAND 24-04-10_CITO_AAA3_FDRT_EV.png 5000000 AAA5 24-04-10 24-04-10_HTHO_AAA5.png 0 1 1 6.698970004336019 True LB 37

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.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
Bas3 3.1 pLAND 24-04-10_CITO_AAA3_FDRT_EV.png 200000000 AAA5 24-04-10 24-04-10_HTHO_AAA5.png 3 7 Y 7000 4.455931955649724 True LB 37

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.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
AAA5 DS-39 True

The final Science supplementary Table S8 maps AAA5 to replicated display name DS-39.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
AAA5 1.0 710.0 WP_042346724.1 AAA+ ATPase 7MCA_I Cell division control protein 6; replication initiation, REPLICATION hhpred_6053627.hhr 53.0 540.0 0.9852 2024-04-15 00:00:00

The final Science supplementary Table S8 reports a high-probability AAA+ ATPase HHpred hit for WP_042346724.1 in AAA5.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
AAA5 1.0 710.0 WP_042346724.1 ZF PF18256.5 HscB_4_cys ; Co-chaperone HscB tetracysteine metal binding motif hhpred_6053627.hhr 583.0 615.0 0.87 2024-04-15 00:00:00

The final Science supplementary Table S8 reports a moderate-probability zinc-finger HHpred hit for WP_042346724.1 in AAA5.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
AAA5 1.0 710.0 WP_042346724.1 HTH 5HS5_B HTH-type transcriptional regulator SarX hhpred_6053627.hhr 623.0 706.0 0.98 2024-04-15 00:00:00

The final Science supplementary Table S8 reports a high-probability HTH HHpred hit for WP_042346724.1 in AAA5.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
| DS-39 | 10\.1101/2025\.01\.08\.631726 | DefensePredictor: A machine learning model to discover novel prokaryotic immune systems |

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.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
| DS-39__DS-39 | | DS-39 | Custom | 200 |

The pinned DefenseFinder HMM inventory records DS-39__DS-39 as a custom DS-39 profile.

DS-39 locus reduces bacteriophage plaquing

Conservative system-level sketch linking the single-gene DS-39 locus to reduced bacteriophage plaquing without resolving DS-39 component function or molecular output.

NONMECHANISTIC · 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.

Edge evidence

DS-39 locus contributes to reduced bacteriophage plaquing RO:0002326
The DS-39/AAA5 locus contributes to reduced bacteriophage plaquing in heterologous E. coli MG1655 plasmid-expression assays.
- DOI:10.1126/science.adv7924 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 DeWeirdt et al. describe the plasmid-based phage challenge used to validate predicted transcriptional units.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx AAA5 NZ_RRWS01000024.1 GCF_003892555.1 + True False True True DefensePredictor hits 12586 14718 MarR family transcriptional regulator WP_042346724.1 9.53722790980957 3.842009204807092 True True Predicted novel defense gene DS-39 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.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx Bas1 3.1 pLAND 24-04-10_CITO_AAA3_FDRT_EV.png 5000000 AAA5 24-04-10 24-04-10_HTHO_AAA5.png 0 1 1 6.698970004336019 True LB 37 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.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx Bas3 3.1 pLAND 24-04-10_CITO_AAA3_FDRT_EV.png 200000000 AAA5 24-04-10 24-04-10_HTHO_AAA5.png 3 7 Y 7000 4.455931955649724 True LB 37 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.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx AAA5 DS-39 True The final Science supplementary Table S8 maps AAA5 to replicated display name DS-39.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx AAA5 1.0 710.0 WP_042346724.1 AAA+ ATPase 7MCA_I Cell division control protein 6; replication initiation, REPLICATION hhpred_6053627.hhr 53.0 540.0 0.9852 2024-04-15 00:00:00 The final Science supplementary Table S8 reports a high-probability AAA+ ATPase HHpred hit for WP_042346724.1 in AAA5.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx AAA5 1.0 710.0 WP_042346724.1 ZF PF18256.5 HscB_4_cys ; Co-chaperone HscB tetracysteine metal binding motif hhpred_6053627.hhr 583.0 615.0 0.87 2024-04-15 00:00:00 The final Science supplementary Table S8 reports a moderate-probability zinc-finger HHpred hit for WP_042346724.1 in AAA5.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx AAA5 1.0 710.0 WP_042346724.1 HTH 5HS5_B HTH-type transcriptional regulator SarX hhpred_6053627.hhr 623.0 706.0 0.98 2024-04-15 00:00:00 The final Science supplementary Table S8 reports a high-probability HTH HHpred hit for WP_042346724.1 in AAA5.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md | DS-39__DS-39 | | DS-39 | Custom | 200 | The pinned DefenseFinder HMM inventory records DS-39__DS-39 as a custom DS-39 profile.
reduced bacteriophage plaquing confers DS-39 system METPO:2007700
DS-39-mediated phage plaquing reduction realizes the DS-39 system trait.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx AAA5 NZ_RRWS01000024.1 GCF_003892555.1 + True False True True DefensePredictor hits 12586 14718 MarR family transcriptional regulator WP_042346724.1 9.53722790980957 3.842009204807092 True True Predicted novel defense gene DS-39 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.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx Bas1 3.1 pLAND 24-04-10_CITO_AAA3_FDRT_EV.png 5000000 AAA5 24-04-10 24-04-10_HTHO_AAA5.png 0 1 1 6.698970004336019 True LB 37 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.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx Bas3 3.1 pLAND 24-04-10_CITO_AAA3_FDRT_EV.png 200000000 AAA5 24-04-10 24-04-10_HTHO_AAA5.png 3 7 Y 7000 4.455931955649724 True LB 37 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.
- DOI:10.1126/science.adv7924 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. The DS nomenclature is used for DefensePredictor discovered systems.
DS-39 system is a phage defense system rdfs:subClassOf
DS-39 system possession is a phage-defense-system trait.
- DOI:10.1126/science.adv7924 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. DeWeirdt et al. name validated TUs as DefensePredictor discovered systems.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md | DS-39 | 10\.1101/2025\.01\.08\.631726 | DefensePredictor: A machine learning model to discover novel prokaryotic immune systems | 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.

Provenance

Identifier source: TraitMech local identifier
Definition source: DOI:10.1126/science.adv7924

Parent traits (1)

phage defense system traitmech:000209

Synonyms (3)

DS-39 EXACT_SYNONYM · DOI:10.1126/science.adv7924
AAA5 RELATED_SYNONYM · https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
DS-39__DS-39 RELATED_SYNONYM · https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md

kg-microbe context

No kg-microbe node embedding matched this record in the 2026-04-25 deepwalk.

Discussions and Knowledge Gaps (1)

Open questions attached to this trait. Seeded by just knowledge-gap-scan and curated; see the corpus-wide index.

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.

KNOWLEDGE GAP OPEN ds-39-defensefinder-model-gap · raised by codex · 2026-09-29

Attached to causal_graphs#ds_39_locus_reduces_phage_plaquing

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

DOI:10.1126/science.adv7924
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.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
AAA5 NZ_RRWS01000024.1 GCF_003892555.1 + True False True True DefensePredictor hits 12586 14718 MarR family transcriptional regulator WP_042346724.1 9.53722790980957 3.842009204807092 True True Predicted novel defense gene DS-39
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
Bas1 3.1 pLAND 24-04-10_CITO_AAA3_FDRT_EV.png 5000000 AAA5 24-04-10 24-04-10_HTHO_AAA5.png 0 1 1 6.698970004336019 True LB 37
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
Bas3 3.1 pLAND 24-04-10_CITO_AAA3_FDRT_EV.png 200000000 AAA5 24-04-10 24-04-10_HTHO_AAA5.png 3 7 Y 7000 4.455931955649724 True LB 37
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
AAA5 DS-39 True
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
AAA5 1.0 710.0 WP_042346724.1 AAA+ ATPase 7MCA_I Cell division control protein 6; replication initiation, REPLICATION hhpred_6053627.hhr 53.0 540.0 0.9852 2024-04-15 00:00:00
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
AAA5 1.0 710.0 WP_042346724.1 ZF PF18256.5 HscB_4_cys ; Co-chaperone HscB tetracysteine metal binding motif hhpred_6053627.hhr 583.0 615.0 0.87 2024-04-15 00:00:00
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
AAA5 1.0 710.0 WP_042346724.1 HTH 5HS5_B HTH-type transcriptional regulator SarX hhpred_6053627.hhr 623.0 706.0 0.98 2024-04-15 00:00:00
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
| DS-39 | 10\.1101/2025\.01\.08\.631726 | DefensePredictor: A machine learning model to discover novel prokaryotic immune systems |
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
| DS-39__DS-39 | | DS-39 | Custom | 200 |
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv

Curation history

2026-09-29T11:35:06Z · MINTED_TRAITMECH_ID · codex
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.
2026-09-29T11:35:07Z · REVIEW_CANONICAL_EXAMPLE_EVIDENCE_GAP · codex
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.