DS-5 system

traitmech:000428 · CLASS · PROPOSED

A phage defense system in which an organism possesses the two-gene DefensePredictor-discovered system 5 locus cataloged as working transcriptional unit PN12 and whose plasmid expression in E. coli MG1655 reduced bacteriophage plaquing.

Trait evidence (10)

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.
DOI:10.1126/science.adv7924
DS-5 is a two protein system that also features a PIN ribonuclease, though not closely related to that of DS-3, along with a second protein containing a DUF5830 and a domain homologous to the anti-CRISPR protein AcrIF4

DeWeirdt et al. describe DS-5 as a two-protein system containing PIN, DUF5830, and AcrIF4-like domains.
DOI:10.1126/science.adv7924
Mutating the catalytic residues in the PIN domain eliminated defense. Deleting the AcrIF4 domain-containing gene also ablated defense by DS-5 but did not lead to unrestrained toxicity of the ribonuclease indicating that DS-5 is likely not a TA system and that both components are essential to defense

DeWeirdt et al. report that DS-5 phage defense requires the predicted PIN catalytic residues and the AcrIF4-domain-containing gene.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
PN12 NZ_QOYG01000008.1 GCF_003333715.1 + True False False True DefensePredictor hits 68231 69878 hypothetical protein, PIN domain-containing protein WP_021513008.1, WP_021513009.1 10.04757221593433 -2.824774475410352 True False Predicted novel defense gene DS-5

The final Science supplementary Table S6 maps working_id PN12 to DS_name DS-5, marks the cloned transcriptional unit as defensive, and records NZ_QOYG01000008.1 positions 68231-69878 with product accessions WP_021513008.1 and WP_021513009.1.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
Bas60 1.2 pLAND 24-03-08_EV_HHHD_PIN2_CRDO.png 5000000 PN12 24-03-09 24-03-09_NTTI_SVIR_PN12_PIN8.png 1 100 1000 3.6989700043360187 True LB 37

The final Science supplementary Table S7 reports a PN12 assay row with a Bas60 phage readout and a -log(EOP) value of 3.699.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
PN12 DS-5 True

The final Science supplementary Table S8 maps PN12 to replicated display name DS-5.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
| DS-5 | 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-5 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-5__DS-5A | | DS-5 | Custom | 50 |

The pinned DefenseFinder HMM inventory records DS-5__DS-5A as a custom DS-5 profile.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
| DS-5__DS-5B | | DS-5 | Custom | 100 |

The pinned DefenseFinder HMM inventory records DS-5__DS-5B as a custom DS-5 profile.

DS-5 locus reduces bacteriophage plaquing

Conservative system-level sketch linking the two-gene DS-5 locus to reduced bacteriophage plaquing without resolving DS-5 component functions or effector activity.

NONMECHANISTIC · The graph captures DS-5 as the validated PN12 transcriptional unit with two product accessions and with DefenseFinder DS-5A and DS-5B profile rows. It does not assert native host breadth, exact profile-to-protein correspondence, the direct viral trigger or substrate, exact PIN-family target, AcrIF4-like component activity, phage target breadth, or DefenseFinder rule-level detection criteria.

Edge evidence

DS-5 locus contributes to reduced bacteriophage plaquing RO:0002326
The DS-5/PN12 locus contributes to reduced bacteriophage plaquing when plasmid expressed.
- 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 validate DefensePredictor-discovered systems by assaying cloned transcriptional units against E. coli phages.
- DOI:10.1126/science.adv7924 Mutating the catalytic residues in the PIN domain eliminated defense. Deleting the AcrIF4 domain-containing gene also ablated defense by DS-5 but did not lead to unrestrained toxicity of the ribonuclease indicating that DS-5 is likely not a TA system and that both components are essential to defense DeWeirdt et al. show that DS-5 protection requires both the predicted PIN catalytic residues and the AcrIF4-domain-containing gene.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx PN12 NZ_QOYG01000008.1 GCF_003333715.1 + True False False True DefensePredictor hits 68231 69878 hypothetical protein, PIN domain-containing protein WP_021513008.1, WP_021513009.1 10.04757221593433 -2.824774475410352 True False Predicted novel defense gene DS-5 The final Science supplementary Table S6 maps working_id PN12 to DS_name DS-5, marks the cloned transcriptional unit as defensive, and records NZ_QOYG01000008.1 positions 68231-69878 with product accessions WP_021513008.1 and WP_021513009.1.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx Bas60 1.2 pLAND 24-03-08_EV_HHHD_PIN2_CRDO.png 5000000 PN12 24-03-09 24-03-09_NTTI_SVIR_PN12_PIN8.png 1 100 1000 3.6989700043360187 True LB 37 The final Science supplementary Table S7 reports a PN12 assay row with a Bas60 phage readout and a -log(EOP) value of 3.699.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md | DS-5__DS-5A | | DS-5 | Custom | 50 | The pinned DefenseFinder HMM inventory records DS-5__DS-5A as a custom DS-5 profile.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md | DS-5__DS-5B | | DS-5 | Custom | 100 | The pinned DefenseFinder HMM inventory records DS-5__DS-5B as a custom DS-5 profile.
reduced bacteriophage plaquing confers DS-5 system METPO:2007700
DS-5-mediated phage plaquing reduction realizes the DS-5 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 each validated transcriptional unit as a DefensePredictor discovered system.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx PN12 NZ_QOYG01000008.1 GCF_003333715.1 + True False False True DefensePredictor hits 68231 69878 hypothetical protein, PIN domain-containing protein WP_021513008.1, WP_021513009.1 10.04757221593433 -2.824774475410352 True False Predicted novel defense gene DS-5 The final Science supplementary Table S6 maps working_id PN12 to DS_name DS-5, marks the cloned transcriptional unit as defensive, and records NZ_QOYG01000008.1 positions 68231-69878 with product accessions WP_021513008.1 and WP_021513009.1.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx Bas60 1.2 pLAND 24-03-08_EV_HHHD_PIN2_CRDO.png 5000000 PN12 24-03-09 24-03-09_NTTI_SVIR_PN12_PIN8.png 1 100 1000 3.6989700043360187 True LB 37 The final Science supplementary Table S7 reports a PN12 assay row with a Bas60 phage readout and a -log(EOP) value of 3.699.
DS-5 system is a phage defense system rdfs:subClassOf
DS-5 system possession is a phage-defense-system trait.
- 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. validate DSs as anti-phage systems.
- https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md | DS-5 | 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-5 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 (4)

DS-5 EXACT_SYNONYM · DOI:10.1126/science.adv7924
PN12 RELATED_SYNONYM · https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
DS-5__DS-5A RELATED_SYNONYM · https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
DS-5__DS-5B 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-5 native host breadth, exact two-component activities, DS-5 profile-to-protein mapping, sensitive-phage breadth, DS-5 PIN nuclease target, AcrIF4-like component function, and rule-level detection criteria before minting narrower DS-5 mechanism children.

KNOWLEDGE GAP OPEN ds-5-defensefinder-model-gap · raised by codex · 2026-09-28

Attached to causal_graphs#ds_5_locus_reduces_phage_plaquing

DeWeirdt et al. support DS-5 as the defensive PN12 transcriptional unit that reduced Bas60 plaquing when cloned in E. coli MG1655, and the pinned DefenseFinder HMM inventory records two DS-5 profile rows. The pinned rules table has no DS-5 row, and the first-pass record does not resolve native host breadth, exact component activities, profile-to-protein mapping, phage target breadth, or endogenous DS-5 activity.

Evidence

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
DOI:10.1126/science.adv7924
DS-5 is a two protein system that also features a PIN ribonuclease, though not closely related to that of DS-3, along with a second protein containing a DUF5830 and a domain homologous to the anti-CRISPR protein AcrIF4
DOI:10.1126/science.adv7924
Mutating the catalytic residues in the PIN domain eliminated defense. Deleting the AcrIF4 domain-containing gene also ablated defense by DS-5 but did not lead to unrestrained toxicity of the ribonuclease indicating that DS-5 is likely not a TA system and that both components are essential to defense
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
PN12 NZ_QOYG01000008.1 GCF_003333715.1 + True False False True DefensePredictor hits 68231 69878 hypothetical protein, PIN domain-containing protein WP_021513008.1, WP_021513009.1 10.04757221593433 -2.824774475410352 True False Predicted novel defense gene DS-5
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
Bas60 1.2 pLAND 24-03-08_EV_HHHD_PIN2_CRDO.png 5000000 PN12 24-03-09 24-03-09_NTTI_SVIR_PN12_PIN8.png 1 100 1000 3.6989700043360187 True LB 37
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
PN12 DS-5 True
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
| DS-5 | 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-5__DS-5A | | DS-5 | Custom | 50 |
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
| DS-5__DS-5B | | DS-5 | Custom | 100 |
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv

Curation history

2026-09-28T07:02:46Z · MINTED_TRAITMECH_ID · codex
Minted DS-5 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 cloned PN12 transcriptional-unit level because the pinned DefenseFinder DS-5 HMM rows are not backed by a rules row; proposals/metpo_traitmech_v305 reserves the replacement placeholder.
2026-09-28T07:02:47Z · REVIEW_CANONICAL_EXAMPLE_EVIDENCE_GAP · codex
Reviewed DS-5 system canonical_examples and left them empty because DeWeirdt et al. support cloned PN12 plaquing assays in E. coli MG1655 plus a DefenseFinder DS-5 model, but not a direct named native microbial isolate exemplar with experimentally verified endogenous DS-5 activity. No paid research was used.
2026-09-28T07:38:24Z · FIX_REVIEW_NOTE · codex
Reworded the DS-5 mutation evidence note after Claude Code Review issue 1387 so it cites the AcrIF4-domain-containing gene rather than asserting a first-gene ordering that the source text and nonmechanistic graph do not establish.