identifier: traitmech:000216 label: Thoeris system definition: A genomics trait describing possession of a Thoeris antiphage defense locus in which phage-triggered TIR-domain proteins generate a cyclic-ADP-ribose-like signal that activates a ThsA NADase effector to deplete NAD and inhibit bacteriophage replication. definition_source: DOI:10.1038/s41586-021-04098-7 trait_category: GENOMICS term_kind: CLASS mapping_status: PROPOSED parent_traits: - traitmech:000209 synonyms: - synonym_text: Thoeris defense system synonym_type: EXACT_SYNONYM source: DOI:10.1038/s41467-020-16703-w - synonym_text: Thoeris defence system synonym_type: EXACT_SYNONYM source: DOI:10.1038/s41586-021-04098-7 evidence: - reference: DOI:10.1038/s41467-020-16703-w snippet: One such system is the Thoeris defense system, which consists of two genes, thsA and thsB notes: Ka et al. support the two-component B. cereus Thoeris system architecture and its standard US-English name. - reference: DOI:10.1038/s41467-020-16703-w snippet: Mutation analysis suggests that NAD+ cleavage is linked to the antiphage function of Thoeris notes: Ka et al. support the relationship between ThsA NADase activity and Thoeris antiphage function. - reference: DOI:10.1038/s41586-021-04098-7 snippet: phage infection triggers Thoeris TIR-domain proteins to produce an isomer of cyclic ADP-ribose notes: Ofir et al. support the phage-triggered TIR-domain signal production that activates the ThsA effector. - reference: DOI:10.1038/s41586-021-04098-7 snippet: This molecular signal activates a second protein, ThsA, which then depletes the cell of the essential molecule nicotinamide adenine dinucleotide (NAD) notes: Ofir et al. connect the Thoeris TIR-domain signal to ThsA NAD depletion. - reference: DOI:10.1038/s41467-020-16703-w snippet: One is from Bacillus cereus MSX-D12. The thsA gene and its downstream thsB gene conferred resistance against myophage infection when engineered into the model bacterium Bacillus subtilis BEST7003 notes: Ka et al. summarize experimental validation of the native Bacillus cereus MSX-D12 Thoeris thsA-thsB locus. canonical_examples: - taxon_id: NCBITaxon:1396 taxon_label: Bacillus cereus note: Ka et al. describe the Bacillus cereus MSX-D12 thsA-thsB Thoeris system that conferred resistance to myophage infection when engineered into a Thoeris-lacking Bacillus subtilis host. reference: DOI:10.1038/s41467-020-16703-w causal_graphs: - graph_id: thoeris_tir_signal_nad_depletion_defense title: Thoeris TIR signalling activates ThsA NAD depletion description: Evidence-backed process sketch linking a Thoeris locus to phage-triggered TIR-domain signalling, ThsA-dependent NAD depletion, and inhibition of bacteriophage replication. scope_status: NONMECHANISTIC scope_notes: The graph captures the characterized Thoeris TIR-signal and ThsA NADase outputs without asserting one universal number of TIR-domain proteins, exact cADPR isomer structure, ThsA oligomeric state, cell-death pathway, or phage trigger across all Thoeris loci. nodes: - node_id: phage_infection label: phage infection node_type: BIOLOGICAL_PROCESS description: Entry and replication attempt by a bacteriophage inside a bacterial host. - node_id: thoeris_locus label: Thoeris locus node_type: GENETIC_ELEMENT description: A Thoeris antiphage defense locus encoding a ThsA NADase effector and one or more Thoeris TIR-domain sensor proteins. - node_id: thoeris_tir_signal_production label: Thoeris TIR cADPR-isomer production node_type: BIOLOGICAL_PROCESS description: Phage-triggered production of a cyclic-ADP-ribose isomer by Thoeris TIR-domain proteins. - node_id: thsa_nad_depletion label: ThsA NAD depletion node_type: BIOLOGICAL_PROCESS description: Thoeris signal-activated ThsA NADase activity that depletes intracellular nicotinamide adenine dinucleotide. - node_id: phage_replication label: phage replication node_type: BIOLOGICAL_PROCESS description: Replication of invading bacteriophage DNA after host-cell entry. - node_id: thoeris_system_trait label: Thoeris system node_type: TRAIT grounding: traitmech:000216 description: Possession of a genome-encoded Thoeris antiphage defense locus. - node_id: phage_defense_system label: phage defense system node_type: TRAIT grounding: traitmech:000209 description: Possession of one or more genome-encoded immune systems that inhibit bacteriophage infection. edges: - subject: thoeris_locus predicate: contributes to predicate_id: RO:0002326 object: thoeris_tir_signal_production description: The Thoeris locus encodes TIR-domain proteins that produce a cADPR-like signal during phage infection. evidence: - reference: DOI:10.1038/s41586-021-04098-7 snippet: phage infection triggers Thoeris TIR-domain proteins to produce an isomer of cyclic ADP-ribose notes: Ofir et al. support Thoeris TIR-domain proteins as phage-triggered cADPR-isomer producers. - subject: phage_infection predicate: activates predicate_id: RO:0002213 object: thoeris_tir_signal_production description: Phage infection activates production of the Thoeris TIR-domain cADPR-like signal. evidence: - reference: DOI:10.1038/s41586-021-04098-7 snippet: phage infection triggers Thoeris TIR-domain proteins to produce an isomer of cyclic ADP-ribose notes: Ofir et al. support phage-triggered Thoeris signal production. - subject: thoeris_tir_signal_production predicate: activates predicate_id: RO:0002213 object: thsa_nad_depletion description: The Thoeris cADPR-like signal activates ThsA, which then depletes cellular NAD. evidence: - reference: DOI:10.1038/s41586-021-04098-7 snippet: This molecular signal activates a second protein, ThsA, which then depletes the cell of the essential molecule nicotinamide adenine dinucleotide (NAD) notes: Ofir et al. connect the TIR-derived signal to ThsA-mediated NAD depletion. - subject: thsa_nad_depletion predicate: mitigates predicate_id: METPO:2007407 object: phage_replication description: ThsA NAD depletion helps inhibit bacteriophage replication. evidence: - reference: DOI:10.1038/s41467-020-16703-w snippet: highlighting a unique strategy for bacterial antiphage resistance via NAD+ degradation notes: Ka et al. place ThsA-linked NAD degradation in Thoeris antiphage resistance. - subject: thsa_nad_depletion predicate: confers predicate_id: METPO:2007700 object: thoeris_system_trait description: ThsA NAD depletion is the antiviral output that realizes the Thoeris system defense phenotype. evidence: - reference: DOI:10.1038/s41586-021-04098-7 snippet: depletes the cell of the essential molecule nicotinamide adenine dinucleotide (NAD) and leads to abortive infection and cell death notes: Ofir et al. support NAD depletion as the Thoeris output that drives abortive infection. - subject: thoeris_system_trait predicate: is a predicate_id: rdfs:subClassOf object: phage_defense_system description: Thoeris system possession is a phage-defense-system trait. evidence: - reference: DOI:10.1038/s41586-021-04098-7 snippet: bacterial anti-phage defence system called Thoeris notes: Ofir et al. place Thoeris in the bacterial antiphage-defense-system family. discussions: - discussion_id: thoeris-family-signal-and-trigger-gap prompt: Resolve Thoeris family architecture, signal chemistry, and phage triggering before minting narrower Thoeris mechanism children. kind: KNOWLEDGE_GAP status: OPEN rationale: Ka et al. support the B. cereus ThsA/ThsB two-gene system and Ofir et al. support the TIR-produced cADPR-like signal that activates ThsA NAD depletion, but Thoeris variants need separate review before TraitMech asserts one exact number of TIR-domain proteins, cADPR-isomer chemistry, TIR target, ThsA activation state, cell-death pathway, or phage-triggering mechanism. posed_by: codex posed_date: '2026-09-15' curation_history: - timestamp: '2026-09-15T13:11:03Z' curator: codex action: MINTED_TRAITMECH_ID changes: Minted Thoeris 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_v93. llm_assisted: true