DS-8 system

traitmech:000432 · CLASS · PROPOSED

A phage defense system in which an organism possesses the single-gene DefensePredictor-discovered system 8 locus cataloged with working_id MNAC and whose plasmid expression in E. coli MG1655 reduced bacteriophage plaquing.

Trait evidence (13)

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
First, we investigated DS-8, a single protein system containing a metallophosphatase domain (Fig. 5A) which is homologous to the human protein SMPDL3A, a phosphodiesterase that cleaves cGAMP to modulate cGAS-STING immunity signaling

DeWeirdt et al. identify DS-8 as a single-protein metallophosphatase-domain system.
DOI:10.1126/science.adv7924
Mutating either of two predicted catalytic residues in the metallophosphatase domain or a residue likely critical to NACHT ATPase activity completely ablated defense by DS-8, indicating that both domains and metallophosphatase activity are essential for protection

DeWeirdt et al. report that predicted metallophosphatase catalytic-residue and NACHT ATPase-residue mutations ablated DS-8 defense.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
MNAC NZ_RRWS01000004.1 GCF_003892555.1 - True False False True DefensePredictor hits 83803 86847 metallophosphoesterase WP_032203427.1 9.394229333124514 6.212606095751518 True True Predicted novel defense gene DS-8

The final Science supplementary Table S6 maps working_id MNAC to DS_name DS-8, marks the cloned transcriptional unit as defensive, and records NZ_RRWS01000004.1 positions 83803-86847 with product accession WP_032203427.1.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
Bas1 1.2 pLAND 24-03-08_EV_HHHD_PIN2_CRDO.png 40000000 MNAC 24-03-08 24-03-08_MNAC_GHOS_BRNT_IMPD.png 1 10 Y 100 5.6020599913279625 True LB 37

The final Science supplementary Table S7 reports an MNAC assay row with a Bas1 phage readout and a -log(EOP) value of 5.602.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
Bas1 A.1 MG1655 24-07-10_EV_MNAC-K375A_MNAC-N84A_MNAC-D52A.png 3000000 MNAC K375A 24-07-10 24-07-10_EV_MNAC-K375A_MNAC-N84A_MNAC-D52A.png 6 3 3000000 0

The final Science supplementary Table S7 reports the MNAC K375A Bas1 mutant row with a -log(EOP) value of 0.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
Bas1 A.1 MG1655 24-07-10_EV_MNAC-K375A_MNAC-N84A_MNAC-D52A.png 3000000 MNAC N84A 24-07-10 24-07-10_EV_MNAC-K375A_MNAC-N84A_MNAC-D52A.png 6 2 2000000 0.1760912591

The final Science supplementary Table S7 reports the MNAC N84A Bas1 mutant row with a -log(EOP) value of 0.176.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
Bas1 A.1 MG1655 24-07-10_EV_MNAC-K375A_MNAC-N84A_MNAC-D52A.png 3000000 MNAC D52A 24-07-10 24-07-10_EV_MNAC-K375A_MNAC-N84A_MNAC-D52A.png 6 4 4000000 -0.1249387366

The final Science supplementary Table S7 reports the MNAC D52A Bas1 mutant row with a -log(EOP) value of -0.125.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
MNAC DS-8 True

The final Science supplementary Table S8 maps MNAC to replicated display name DS-8.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
MNAC 1.0 1014.0 WP_032203427.1 Metallophosphatase 5KAR_A Acid sphingomyelinase-like phosphodiesterase 3b; phosphoesterase, extracellular, membrane hhpred_8521728.hhr 1.0 275.0 0.997 2024-04-16 00:00:00

The final Science supplementary Table S8 reports a metallophosphatase HHpred hit for WP_032203427.1 in MNAC.
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
MNAC 1.0 1014.0 WP_032203427.1 NACHT 8FML_A Baculoviral IAP repeat-containing protein 1e; Inflammasome, Innate immunity, Bacterial ligand, host-pathogen interaction, Protein complex, IMMUNE SYSTEM hhpred_8521728.hhr 331.0 734.0 1.0 2024-04-16 00:00:00

The final Science supplementary Table S8 reports a NACHT HHpred hit for WP_032203427.1 in MNAC.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
| DS-8 | 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-8 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-8__DS-8 | | DS-8 | Custom | 200 |

The pinned DefenseFinder HMM inventory records DS-8__DS-8 as a custom DS-8 profile.

DS-8 locus reduces bacteriophage plaquing

Conservative system-level sketch linking the single-gene DS-8 locus to reduced bacteriophage plaquing without resolving DS-8 component function or effector activity.

NONMECHANISTIC · The graph captures DS-8 as the validated MNAC transcriptional unit with one product accession and with a DefenseFinder DS-8 profile row. It does not assert native host breadth, exact profile-to-protein correspondence, the direct viral trigger or cyclic-nucleotide substrate, the exact NACHT-mediated activation step, relationship to NLR-like bNACHT systems, phage target breadth, or DefenseFinder rule-level detection criteria.

Edge evidence

DS-8 locus contributes to reduced bacteriophage plaquing RO:0002326
The DS-8/MNAC locus contributes to reduced bacteriophage plaquing when plasmid expressed.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx MNAC NZ_RRWS01000004.1 GCF_003892555.1 - True False False True DefensePredictor hits 83803 86847 metallophosphoesterase WP_032203427.1 9.394229333124514 6.212606095751518 True True Predicted novel defense gene DS-8 The final Science supplementary Table S6 maps working_id MNAC to DS_name DS-8, marks the cloned transcriptional unit as defensive, and records NZ_RRWS01000004.1 positions 83803-86847 with product accession WP_032203427.1.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx Bas1 1.2 pLAND 24-03-08_EV_HHHD_PIN2_CRDO.png 40000000 MNAC 24-03-08 24-03-08_MNAC_GHOS_BRNT_IMPD.png 1 10 Y 100 5.6020599913279625 True LB 37 The final Science supplementary Table S7 reports an MNAC assay row with a Bas1 phage readout and a -log(EOP) value of 5.602.
reduced bacteriophage plaquing confers DS-8 system METPO:2007700
DS-8-mediated phage plaquing reduction realizes the DS-8 system trait.
- DOI:10.1126/science.adv7924 First, we investigated DS-8, a single protein system containing a metallophosphatase domain (Fig. 5A) which is homologous to the human protein SMPDL3A, a phosphodiesterase that cleaves cGAMP to modulate cGAS-STING immunity signaling DeWeirdt et al. identify DS-8 as a single-protein metallophosphatase-domain system.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx MNAC NZ_RRWS01000004.1 GCF_003892555.1 - True False False True DefensePredictor hits 83803 86847 metallophosphoesterase WP_032203427.1 9.394229333124514 6.212606095751518 True True Predicted novel defense gene DS-8 The final Science supplementary Table S6 maps working_id MNAC to DS_name DS-8, marks the cloned transcriptional unit as defensive, and records NZ_RRWS01000004.1 positions 83803-86847 with product accession WP_032203427.1.
- https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx Bas1 1.2 pLAND 24-03-08_EV_HHHD_PIN2_CRDO.png 40000000 MNAC 24-03-08 24-03-08_MNAC_GHOS_BRNT_IMPD.png 1 10 Y 100 5.6020599913279625 True LB 37 The final Science supplementary Table S7 reports an MNAC assay row with a Bas1 phage readout and a -log(EOP) value of 5.602.
DS-8 system is a phage defense system rdfs:subClassOf
DS-8 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-8 | 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-8 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-8 EXACT_SYNONYM · DOI:10.1126/science.adv7924
MNAC RELATED_SYNONYM · https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
DS-8__DS-8 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-8 native host breadth, DS-8 profile-to-protein mapping, sensitive-phage breadth, direct cyclic-nucleotide substrate, NACHT-mediated activation route, relationship to NLR-like bNACHT systems, and rule-level detection criteria before minting narrower DS-8 mechanism children.

KNOWLEDGE GAP OPEN ds-8-defensefinder-model-gap · raised by codex · 2026-09-28

Attached to causal_graphs#ds_8_locus_reduces_phage_plaquing

DeWeirdt et al. support DS-8 as the defensive MNAC transcriptional unit that reduced Bas1 plaquing when cloned in E. coli MG1655, identify DS-8 as a single-protein system with metallophosphatase and NACHT domains, and report that D52A, N84A, and K375A mutations ablated Bas1 protection. The pinned DefenseFinder HMM inventory records one DS-8 profile row. The pinned rules table has no DS-8 row, and the first-pass record does not resolve native host breadth, exact profile-to-protein correspondence, direct cyclic-nucleotide substrate, exact NACHT-mediated activation route, phage target breadth, endogenous DS-8 activity, or whether DS-8 should be related to the broader NLR-like bNACHT system family.

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
First, we investigated DS-8, a single protein system containing a metallophosphatase domain (Fig. 5A) which is homologous to the human protein SMPDL3A, a phosphodiesterase that cleaves cGAMP to modulate cGAS-STING immunity signaling
DOI:10.1126/science.adv7924
Mutating either of two predicted catalytic residues in the metallophosphatase domain or a residue likely critical to NACHT ATPase activity completely ablated defense by DS-8, indicating that both domains and metallophosphatase activity are essential for protection
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
MNAC NZ_RRWS01000004.1 GCF_003892555.1 - True False False True DefensePredictor hits 83803 86847 metallophosphoesterase WP_032203427.1 9.394229333124514 6.212606095751518 True True Predicted novel defense gene DS-8
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
Bas1 1.2 pLAND 24-03-08_EV_HHHD_PIN2_CRDO.png 40000000 MNAC 24-03-08 24-03-08_MNAC_GHOS_BRNT_IMPD.png 1 10 Y 100 5.6020599913279625 True LB 37
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
Bas1 A.1 MG1655 24-07-10_EV_MNAC-K375A_MNAC-N84A_MNAC-D52A.png 3000000 MNAC K375A 24-07-10 24-07-10_EV_MNAC-K375A_MNAC-N84A_MNAC-D52A.png 6 3 3000000 0
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
Bas1 A.1 MG1655 24-07-10_EV_MNAC-K375A_MNAC-N84A_MNAC-D52A.png 3000000 MNAC N84A 24-07-10 24-07-10_EV_MNAC-K375A_MNAC-N84A_MNAC-D52A.png 6 2 2000000 0.1760912591
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
Bas1 A.1 MG1655 24-07-10_EV_MNAC-K375A_MNAC-N84A_MNAC-D52A.png 3000000 MNAC D52A 24-07-10 24-07-10_EV_MNAC-K375A_MNAC-N84A_MNAC-D52A.png 6 4 4000000 -0.1249387366
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
MNAC DS-8 True
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
MNAC 1.0 1014.0 WP_032203427.1 Metallophosphatase 5KAR_A Acid sphingomyelinase-like phosphodiesterase 3b; phosphoesterase, extracellular, membrane hhpred_8521728.hhr 1.0 275.0 0.997 2024-04-16 00:00:00
https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
MNAC 1.0 1014.0 WP_032203427.1 NACHT 8FML_A Baculoviral IAP repeat-containing protein 1e; Inflammasome, Innate immunity, Bacterial ligand, host-pathogen interaction, Protein complex, IMMUNE SYSTEM hhpred_8521728.hhr 331.0 734.0 1.0 2024-04-16 00:00:00
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
| DS-8 | 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-8__DS-8 | | DS-8 | Custom | 200 |
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv

Curation history

2026-09-28T10:43:27Z · MINTED_TRAITMECH_ID · codex
Minted DS-8 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 MNAC transcriptional-unit level because the pinned DefenseFinder DS-8 HMM row is not backed by a rules row; proposals/metpo_traitmech_v309 reserves the replacement placeholder.
2026-09-28T10:43:28Z · REVIEW_CANONICAL_EXAMPLE_EVIDENCE_GAP · codex
Reviewed DS-8 system canonical_examples and left them empty because DeWeirdt et al. support cloned MNAC plaquing assays in E. coli MG1655 plus a DefenseFinder DS-8 model, but not a direct named native microbial isolate exemplar with experimentally verified endogenous DS-8 activity. No paid research was used.
2026-09-28T11:24:51Z · ADDRESS_REVIEW_FINDINGS · codex
Addressed PR review issues #1397 and #1398 by replacing the ambiguous generic DS naming quote with DS-8-specific single-protein and catalytic-mutant article snippets, adding final Science Table S7 MNAC K375A/N84A/D52A Bas1 mutant evidence, and narrowing the open DS-8 knowledge gap to substrate identity, NACHT-mediated activation route, native-host and phage breadth, exact profile mapping, and DefenseFinder rule-level criteria.