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phosphorothioate defense system

traitmech:000213 · CLASS · PROPOSED

A genomics trait describing possession of a DNA phosphorothioation-dependent antiviral locus in which host DNA phosphorothioate modification is paired with a Dnd-, Ssp-, or Pbe-family effector module to restrict invading viral DNA.

Trait evidence (5)

  • DOI:10.1038/s41564-020-0700-6
    We previously identified the Dnd system, which uses DndABCDE to insert sulfur into the DNA backbone as a double-stranded phosphorothioate (PT) modification, and DndFGH, a restriction component

    Xiong et al. summarize the Dnd modification and restriction modules as a DNA phosphorothioation defense system.

  • DOI:10.1038/s41564-020-0700-6
    SspABCD coupled with SspE provides protection against phages

    Xiong et al. support SspABCD-SspE as a bacterial phosphorothioation-sensing antiphage defense system.

  • DOI:10.1128/mbio.00933-23
    Usually, this modification gene cluster is paired with a restriction module consisting of DndF, DndG, and DndH

    Jiang et al. support the paired modification-plus-restriction architecture of Dnd-related phosphorothioate R-M systems.

  • DOI:10.1128/mbio.00933-23
    the host could benefit from the protection provided by Dnd-related R-M systems against infection by various lytic phages as well as temperate phages

    Jiang et al. experimentally demonstrated broad antiphage protection by Dnd-related phosphorothioate R-M systems.

  • DOI:10.1038/s41467-019-09390-9
    DndCDEA-specific DNA phosphorothioate (PT) modification and the PbeABCD-mediated halt of virus propagation

    Xiong et al. support DndCDEA-PbeABCD as an archaeal phosphorothioation-dependent antiviral branch distinct from bacterial DndFGH and Ssp systems.

Phosphorothioate restriction modules target invading viral DNA

Evidence-backed process sketch linking host DNA phosphorothioate modification to PT-dependent self/non-self discrimination, restriction of invading viral DNA, and impaired viral DNA replication.

NONMECHANISTIC · The graph captures system-level logic shared by phosphorothioate-based Dnd, Ssp, and Pbe antiviral systems without claiming that DndFGH, SspE, SspFGH, and PbeABCD sense PT marks, damage foreign DNA, or inhibit viral replication by one exact protein mechanism.

Phosphorothioate restriction modules target invading viral DNA Interactive directed graph showing evidence-backed causal relationships for phosphorothioate defense system.

Edge evidence

  • phosphorothioate modification module contributes to DNA phosphorothioation RO:0002326

    DndABCDE or SspABCD modification modules install sequence-specific phosphorothioate marks on host DNA.

    • DOI:10.1038/s41564-020-0700-6 uses DndABCDE to insert sulfur into the DNA backbone as a double-stranded phosphorothioate (PT) modification Xiong et al. support DndABCDE-dependent host DNA phosphorothioation.
    • DOI:10.1038/s41564-020-0700-6 SspABCD confers single-stranded and high-frequency PTs with SspB acting as a nickase Xiong et al. support SspABCD-dependent host DNA phosphorothioation.
  • DNA phosphorothioation contributes to PT-dependent foreign DNA targeting RO:0002326

    Sequence-specific PT marks couple host DNA modification to PT-dependent self/non-self restriction by Dnd-, Ssp-, and Pbe-family effector modules.

    • DOI:10.1038/s41564-020-0700-6 SspE senses sequence-specific PTs by virtue of its PT-stimulated NTPase activity to exert its anti-phage activity Xiong et al. support direct coupling between sequence-specific PT marks and SspE restriction activity.
  • PT-dependent foreign DNA targeting activates viral DNA restriction RO:0002213

    Dnd, Ssp, and Pbe phosphorothioation-dependent systems converge on restriction of viral DNA lacking host PT marks.

    • DOI:10.1038/s41564-020-0700-6 SspE inhibits phage propagation by introducing nicking damage to impair phage DNA replication Xiong et al. support SspE-linked nicking damage as a second PT-dependent route to restricted phage replication.
    • DOI:10.1128/mbio.00933-23 DndF, DndG, and DndH undergoes conformational changes to perform DNA binding, translocation, and DNA nicking activities and scavenge the foreign DNA Jiang et al. summarize DndFGH-mediated DNA binding, translocation, and nicking of foreign DNA that lacks PT modification.
    • DOI:10.1038/s41467-019-09390-9 PbeABCD exerted antiviral activity depending on the presence of PT modifications Xiong et al. support PT-dependent PbeABCD antiviral activity.
  • viral DNA restriction mitigates viral DNA replication METPO:2007407

    PT-dependent effector activity inhibits replication of invading viral DNA.

    • DOI:10.1038/s41564-020-0700-6 SspE inhibits phage propagation by introducing nicking damage to impair phage DNA replication Xiong et al. directly connect SspE DNA nicking to impaired phage replication.
    • DOI:10.1038/s41467-019-09390-9 PbeABCD-mediated halt of virus propagation via inhibition of DNA replication Xiong et al. connect PbeABCD-dependent PT restriction to inhibited archaeal viral DNA replication.
  • viral DNA restriction confers phosphorothioate defense system METPO:2007700

    Restriction of invading viral DNA realizes phosphorothioate-based antiviral defense.

    • DOI:10.1128/mbio.00933-23 the host could benefit from Dnd-related R-M systems for a broad range of antiphage activities Jiang et al. support Dnd-mediated phosphorothioate restriction as an antiphage defense output.
    • DOI:10.1038/s41467-019-09390-9 a new type of PT-based virus resistance system Xiong et al. place DndCDEA-PbeABCD in the PT antiviral defense family.
  • phosphorothioate defense system is a phage defense system rdfs:subClassOf

    Phosphorothioate restriction-system possession is an antiviral defense-system trait.

Provenance

Identifier source
TraitMech local identifier
Definition source
DOI:10.1038/s41564-020-0700-6

Parent traits (1)

Children (4)

Synonyms (2)

  • PT-associated R-M system EXACT_SYNONYM · DOI:10.1128/mbio.00933-23
  • PT-related R-M system EXACT_SYNONYM · DOI:10.1128/mbio.00933-23

kg-microbe context

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

Canonical examples (1)

Organisms cited as exemplars of this trait. Taxon ids are NCBITaxon and link out to the NCBI record.

  • Escherichia coli B7A NCBITaxon:340184 DOI:10.1128/mbio.00933-23 Jiang et al. cloned the native E. coli B7A dndBCDE-FGH module into E. coli DH10B and measured strong DndB7A R-M protection against multiple lytic phages.

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 archaeal phosphorothioate-based antiviral systems before minting additional narrower children under the phosphorothioate defense parent.

KNOWLEDGE GAP RESOLVED phosphorothioate-subfamily-split-gap · raised by codex · 2026-09-15

Not yet attached to a section of this record — a curator sets attaches_to (e.g. causal_graphs#some_edge) so the gap shows beside the mechanism it concerns.

Dnd, SspABCD-SspE, SspABCD-SspFGH, and archaeal DndCDEA-PbeABCD PT antiviral architectures have all been split out as narrower phosphorothioate defense system children.

Curation history

  1. · MINTED_TRAITMECH_ID · codex

    Minted phosphorothioate defense system as a DOI-backed GENOMICS TraitRecord under the phage defense system parent after an ignored-and-hidden duplicate review found no exact live TraitMech, METPO, or prior proposal record; the replacement placeholder is reserved in proposals/metpo_traitmech_v90.

  2. · RESOLVE_DISCUSSION_SCOPE · codex

    Removed Dnd from the open phosphorothioate subfamily split-gap discussion after minting traitmech:000221 for the Dnd system; SspE, SspFGH, and archaeal phosphorothioate-based antiviral systems remain open.

  3. · RESOLVE_DISCUSSION_SCOPE · codex

    Removed SspBCD-E from the open phosphorothioate subfamily split-gap discussion after minting traitmech:000222 for the SspABCD-SspE system; SspFGH and archaeal phosphorothioate-based antiviral systems remain open.

  4. · RESOLVE_DISCUSSION_SCOPE · codex

    Removed SspFGH from the open phosphorothioate subfamily split-gap discussion after minting traitmech:000223 for the SspABCD-SspFGH system; archaeal phosphorothioate-based antiviral systems remain open.

  5. · RESOLVE_DISCUSSION_SCOPE · codex

    Minted traitmech:000224 for the archaeal DndCDEA-PbeABCD system, broadened the phosphorothioate defense system parent from bacteriophage-only Dnd/Ssp wording to Dnd/Ssp/Pbe viral-DNA restriction wording, and marked the phosphorothioate subfamily split-gap discussion resolved.