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Pycsar system

traitmech:000236 · CLASS · PROPOSED

A phage defense system in which an organism possesses a Pycsar locus encoding a PycC pyrimidine cyclase and a cognate cyclic-pyrimidine receptor effector whose phage-induced cyclic CMP or cyclic UMP signaling activates antiviral effector outputs that inhibit bacteriophage propagation.

Trait evidence (7)

  • DOI:10.1016/j.cell.2021.09.031
    We discovered a family of bacterial pyrimidine cyclase enzymes that specifically synthesize cCMP and cUMP following phage infection

    Tal et al. support Pycsar-associated pyrimidine cyclases as phage-induced producers of cyclic CMP and cyclic UMP.

  • DOI:10.1016/j.cell.2021.09.031
    The cCMP and cUMP molecules then activate effector proteins

    Tal et al. connect cyclic pyrimidine second messengers to activation of Pycsar effector proteins.

  • DOI:10.1016/j.cell.2021.09.031
    The predicted cyclase genes are usually found in an operon together with an additional gene, and we therefore cloned such two-gene operons, one from Escherichia coli 303145 and the other from E. coli E831, into the laboratory E. coli strain MG1655. Challenging the transformed bacteria with a panel of 12 phages showed that both operons provided substantial defense against multiple phages

    Tal et al. support a canonical Escherichia coli example by showing that two E. coli Pycsar loci conferred antiphage defense after cloning into E. coli MG1655.

  • DOI:10.1016/j.cell.2021.09.031
    Mutation in the predicted active site of the cyclase domain abolished defense

    Tal et al. support the functional importance of the PycC cyclase domain for the antiphage phenotype.

  • DOI:10.1038/s41467-024-49861-2
    This system consists of a pyrimidine cyclase and a cyclic pyrimidine receptor protein

    Hou et al. support defining Pycsar systems around a pyrimidine cyclase plus a cognate cyclic-pyrimidine receptor rather than a bare pycC gene.

  • DOI:10.1038/s41467-024-49861-2
    a distinct zinc-finger motif of the uridylate cyclase is identified to confer substantial resistance against phage infections

    Hou et al. support the uridylate-cyclase branch while the broad TraitRecord leaves cCMP-producing and cUMP-producing Pycsar clades unresolved as children.

  • DOI:10.1038/s41467-024-49861-2
    structural characterization of cUMP receptor protein PycTIR provides clear picture of specific cUMP recognition and identifies a conserved N-terminal extension that mediates PycTIR oligomerization and activation

    Hou et al. support cyclic UMP recognition by the PycTIR cyclic-pyrimidine receptor as one resolved Pycsar effector-activation mechanism.

Pycsar loci couple cyclic-pyrimidine signaling to phage defense

Evidence-backed process sketch linking a complete Pycsar locus to phage-induced PycC pyrimidine cyclase activity, cyclic CMP or cyclic UMP signaling, cyclic-pyrimidine receptor activation, antiviral effector output, and inhibition of phage propagation.

NONMECHANISTIC · The graph stays at the Pycsar-family level and uses characterized cytidylate-cyclase and uridylate-cyclase examples without asserting one universal cyclase clade, cCMP-versus-cUMP product, PycTIR-versus-PycTM effector fold, AGS-C role, zinc-finger role, activating phage trigger, membrane impairment, or NAD-depletion output across all Pycsar antiphage loci.

Pycsar loci couple cyclic-pyrimidine signaling to phage defense Interactive directed graph showing evidence-backed causal relationships for Pycsar system.

Edge evidence

  • Pycsar locus contributes to phage-induced PycC cyclase activity RO:0002326

    Pycsar loci encode a PycC pyrimidine cyclase whose catalytic activity is required for the antiphage phenotype.

    • DOI:10.1016/j.cell.2021.09.031 Mutation in the predicted active site of the cyclase domain abolished defense Tal et al. show that the PycC active site is required for defense in an E. coli Pycsar locus.
  • Pycsar locus contributes to cyclic pyrimidine receptor activation RO:0002326

    Complete Pycsar systems pair the PycC cyclase with a cyclic-pyrimidine receptor effector.

    • DOI:10.1038/s41467-024-49861-2 This system consists of a pyrimidine cyclase and a cyclic pyrimidine receptor protein Hou et al. support a two-part system definition rather than a cyclase-only sequence feature.
  • phage-induced PycC cyclase activity contributes to cyclic pyrimidine second messenger synthesis RO:0002326

    PycC pyrimidine cyclases synthesize cyclic CMP or cyclic UMP after phage infection.

    • DOI:10.1016/j.cell.2021.09.031 We discovered a family of bacterial pyrimidine cyclase enzymes that specifically synthesize cCMP and cUMP following phage infection Tal et al. link PycC cyclase activity to phage-induced cyclic CMP and cyclic UMP production.
  • cyclic pyrimidine second messenger synthesis activates cyclic pyrimidine receptor activation RO:0002213

    Cyclic CMP and cyclic UMP second messengers can activate Pycsar effector proteins.

    • DOI:10.1016/j.cell.2021.09.031 The cCMP and cUMP molecules then activate effector proteins Tal et al. support cyclic-pyrimidine second messengers as direct activators of Pycsar effector proteins.
  • cyclic pyrimidine receptor activation contributes to Pycsar antiviral output RO:0002326

    Pycsar receptor activation stimulates an immune-effector state that antagonizes phage infection.

    • DOI:10.1016/j.cell.2021.09.031 We discovered a family of bacterial pyrimidine cyclase enzymes that specifically synthesize cCMP and cUMP following phage infection and demonstrate that these molecules activate immune effectors that execute an antiviral response Tal et al. connect cCMP and cUMP to immune-effector activation and antiviral output.
  • Pycsar antiviral output mitigates phage propagation METPO:2007407

    Native E. coli Pycsar systems substantially defend against multiple bacteriophages.

    • DOI:10.1016/j.cell.2021.09.031 The predicted cyclase genes are usually found in an operon together with an additional gene, and we therefore cloned such two-gene operons, one from Escherichia coli 303145 and the other from E. coli E831, into the laboratory E. coli strain MG1655. Challenging the transformed bacteria with a panel of 12 phages showed that both operons provided substantial defense against multiple phages Tal et al. demonstrated substantial antiphage defense by two native E. coli Pycsar operons cloned into E. coli MG1655.
  • Pycsar antiviral output confers Pycsar system METPO:2007700

    Cyclic-pyrimidine signaling through a Pycsar receptor realizes the Pycsar antiphage trait.

    • DOI:10.1038/s41467-024-49861-2 named pyrimidine cyclase system for anti-phage resistance (Pycsar) Hou et al. connect the Pycsar name to the cyclic-pyrimidine signaling system's antiphage-resistance phenotype.
  • Pycsar system is a phage defense system rdfs:subClassOf

    Pycsar system possession is a phage-defense-system trait.

    • DOI:10.1016/j.cell.2021.09.031 cCMP/cUMP cyclases function as part of a family of bacterial anti-phage defense systems Tal et al. support Pycsar system as a child of phage defense system.

Provenance

Identifier source
TraitMech local identifier
Definition source
DOI:10.1016/j.cell.2021.09.031

Parent traits (1)

Synonyms (2)

  • Pyrimidine Cyclase System for Antiphage Resistance EXACT_SYNONYM · DOI:10.1016/j.cell.2021.09.031
  • pyrimidine cyclase system for anti-phage resistance EXACT_SYNONYM · DOI:10.1038/s41467-024-49861-2

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 NCBITaxon:562 DOI:10.1016/j.cell.2021.09.031 Tal et al. cloned native Pycsar two-gene operons from E. coli 303145 and E. coli E831 into E. coli MG1655 and showed that both operons provided substantial defense against multiple 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 Pycsar cyclase clades, cyclic pyrimidine specificity, receptor-effector folds, activating phage triggers, and effector outputs before minting narrower Pycsar subtype children.

KNOWLEDGE GAP OPEN pycsar-signal-and-effector-gap · raised by codex · 2026-09-18

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.

Tal et al. support Pycsar systems as widespread PycC-containing antiphage systems whose phage-induced cyclic CMP or cyclic UMP second messengers activate immune effectors, and Hou et al. resolve a uridylate-cyclase/PycTIR branch with zinc-finger and cUMP-recognition determinants. The first TraitRecord therefore stays at the broad Pycsar-system level until separate subtype review resolves which cyclase clades, second messengers, receptor folds, phage triggers, and outputs apply across each family.

Curation history

  1. · MINTED_TRAITMECH_ID · codex

    Minted Pycsar 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_v113.