DS-6 system

Edge evidence

• DS-6 locus contributes to reduced bacteriophage plaquing RO:0002326

  The DS-6/HIPA 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.
  • https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx HIPA NZ_QOWQ01000062.1 GCF_003334335.1 - True False True True DefensePredictor hits 1591 3164 DUF3037 domain-containing protein, hypothetical protein WP_000210934.1, WP_000389051.1 6.427268761356274 -2.428836967683248 True False Predicted novel defense gene DS-6 The final Science supplementary Table S6 maps working_id HIPA to DS_name DS-6, marks the cloned transcriptional unit as defensive, and records NZ_QOWQ01000062.1 positions 1591-3164 with product accessions WP_000210934.1 and WP_000389051.1.
  • 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 HIPA 24-03-08 24-03-08_IMPD_DISA_2CM2_MAZF.png 3 5 Y 5000 3.9030899869919438 True True LB 37 The final Science supplementary Table S7 reports a HIPA assay row with a Bas1 phage readout, smaller plaques, and a -log(EOP) value of 3.903.
  • DOI:10.1126/science.adv7924 When we mutated a key predicted catalytic residue in DS-6A, we observed a loss of defense, suggesting that kinase activity is essential for protection. DeWeirdt et al. report that DS-6A catalytic residue mutagenesis caused loss of defense.
  • 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 HIPA 24-07-12 24-07-12_HIPA_HIPA-D139A_SVIR_SVIR-H52A_DISA_DISA-D433A.png 1 2 20 5.176091259 Bas1 A.1 MG1655 24-07-10_EV_MNAC-K375A_MNAC-N84A_MNAC-D52A.png 3000000 HIPA D139A 24-07-12 24-07-12_HIPA_HIPA-D139A_SVIR_SVIR-H52A_DISA_DISA-D433A.png 5 4 400000 0.8750612634 The final Science supplementary Table S7 System Mutants sheet pairs wild-type HIPA and HIPA D139A in a Bas1 assay panel, with -log(EOP) shifting from 5.176 to 0.875 for the D139A catalytic mutant.
  • https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx Bas1 B.1 MG1655 24-07-17_MVB1_VPUS_VAME_EV.png 3000000 HIPA 24-07-18 24-07-18_IMPD-Y157A_IMPD_IMPD-R330A_IMPD-H335A_HIPA_HIPA-D139A.png 2 10 1000 3.477121255 Bas1 B.1 MG1655 24-07-17_MVB1_VPUS_VAME_EV.png 3000000 HIPA D139A 24-07-18 24-07-18_IMPD-Y157A_IMPD_IMPD-R330A_IMPD-H335A_HIPA_HIPA-D139A.png 6 4 4000000 -0.1249387366 The final Science supplementary Table S7 System Mutants sheet records a second HIPA versus HIPA D139A Bas1 panel, with -log(EOP) shifting from 3.477 to -0.125 for the D139A catalytic mutant.
• reduced bacteriophage plaquing confers DS-6 system METPO:2007700

  DS-6-mediated phage plaquing reduction realizes the DS-6 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 HIPA NZ_QOWQ01000062.1 GCF_003334335.1 - True False True True DefensePredictor hits 1591 3164 DUF3037 domain-containing protein, hypothetical protein WP_000210934.1, WP_000389051.1 6.427268761356274 -2.428836967683248 True False Predicted novel defense gene DS-6 The final Science supplementary Table S6 maps working_id HIPA to DS_name DS-6, marks the cloned transcriptional unit as defensive, and records NZ_QOWQ01000062.1 positions 1591-3164 with product accessions WP_000210934.1 and WP_000389051.1.
  • 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 HIPA 24-03-08 24-03-08_IMPD_DISA_2CM2_MAZF.png 3 5 Y 5000 3.9030899869919438 True True LB 37 The final Science supplementary Table S7 reports a HIPA assay row with a Bas1 phage readout, smaller plaques, and a -log(EOP) value of 3.903.
• DS-6 system is a phage defense system rdfs:subClassOf

  DS-6 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-6 | 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-6 source key to the preprint DOI for the DeWeirdt et al. DefensePredictor study, which has since been published in Science.