id: MODULE:phage_temperate_latency_switch title: Temperate Bacteriophage Lysis-Lysogeny Decision, Prophage Integration, and Induction description: 'A reusable module capturing the regulatory decision (`GO:0098689`), establishment (`GO:0019043`), maintenance (`GO:0019044`), and induction/release (`GO:0019046`, `GO:0032359`) of viral latency (lysogeny) in temperate bacteriophages. Two orthogonal variant axes are modeled: (1) the bistable lysis-lysogeny decision circuit (`CI`/`Cro`/`CII`/`CIII` host-protease sensing in lambdoid phages, `C` repressor/Cox switch in P2-like phages, and the arbitrium `AimP`/`AimR`/`AimX` peptide quorum-sensing circuit in Bacillus SPbeta/phi3T phages), and (2) the prophage maintenance state (`GO:0075713` site-specific integrated chromosomal prophage via tyrosine/serine integrase vs. `GO:0075720` extrachromosomal circular or `GO:0075530` linear telomeric plasmid prophage in P1 and N15 vs. replicative transposition prophage integration via DDE transposase `GO:0004803` / `GO:0015074` in Mu-like phages).' status: COMPLETE scope: CONCRETE evidence: - source_id: PMID:28099413 title: Communication between viruses guides lysis-lysogeny decisions. statement: Bacillus phages phi3T and SPbeta use the arbitrium peptide signaling system (AimP peptide, AimR receptor transcription factor, and AimX non-coding RNA regulator) to guide the lysis-lysogeny decision across infection cycles. supporting_text: Here we show that viruses (phages) of the SPbeta group use a small-molecule communication system to coordinate lysis-lysogeny decisions. - source_id: file:projects/PHAGES.md title: Bacteriophage Genome & Module Curation Plan statement: Defines the temperate phage latency-replication decision and prophage maintenance variant sets and notes that GO uses general viral latency terms (`GO:0019042`) in place of "lysogeny". supporting_text: In phages, the **temperate latency module** (`GO:0098689` latency-replication decision, `GO:0075713` proviral integration, `GO:0032359` provirus excision) is **biologically absent** in obligately lytic genomes (T4, T7, φX174, MS2, φ29). notes: Curated for the Bacteriophage Genome & Module Curation project. Gene Ontology does not contain terms labeled "lysogeny" or "prophage induction"; temperate phage curators must use the viral latency hierarchy (`GO:0098689` latency-replication decision, `GO:0019042` viral latency, `GO:0019043` establishment of viral latency, `GO:0075713` establishment of integrated proviral latency, `GO:0075720` establishment of episomal latency, `GO:0075530` establishment of latency as a linear episome, `GO:0019044` maintenance of viral latency, `GO:0019046` release from viral latency, and `GO:0032359` provirus excision). module: id: phage_temperate_latency_switch label: Temperate Bacteriophage Lysis-Lysogeny Switch and Prophage Maintenance module_type: BIOLOGICAL_PROCESS concepts: - preferred_term: latency-replication decision term: id: GO:0098689 label: latency-replication decision description: Regulatory decision by a temperate bacteriophage between entering the lytic reproductive cycle or establishing dormant prophage latency. - preferred_term: viral latency term: id: GO:0019042 label: viral latency description: Dormant persistence of the phage genome within the bacterial host (lysogeny). - preferred_term: release from viral latency term: id: GO:0019046 label: release from viral latency description: Reactivation (prophage induction) of a dormant prophage into the lytic cycle. context: taxa: - preferred_term: Viruses term: id: NCBITaxon:10239 label: Viruses - preferred_term: Bacteria term: id: NCBITaxon:2 label: Bacteria variant_sets: - id: lysis_lysogeny_decision_circuit label: Temperate phage lysis-lysogeny decision circuit axis: regulatory signal integration and transcriptional switch selection: EXACTLY_ONE notes: Temperate phages evaluate host physiological state, multiplicity of infection, or extracellular phage-encoded peptide concentration to choose between lytic replication and lysogenic latency. variants: - id: lambdoid_cII_cI_cro_bistable_switch label: Lambdoid CII/CIII host-protease sensing and CI-Cro bistable switch (lambda/P22-type) module_type: BIOLOGICAL_PROCESS description: Phage-encoded CIII inhibits host FtsH (HflB) protease to stabilize the CII transcriptional activator at high multiplicity of infection; CII activates the pRE, pI, and paQ promoters to express the CI master repressor and Int integrase while Cro competes at oR/oL to drive lytic gene expression. parts: - order: 1 role: CII/CIII commitment to latency establishment node: id: cii_ciii_latency_commitment label: CII transcriptional activation and CIII protease inhibition module_type: BIOLOGICAL_PROCESS annotons: - id: cii_activator_activity label: CII activation of lysogenic promoters pRE, pI, and paQ participant: selector_type: ANY_WITH_FUNCTION required_function: preferred_term: DNA-binding transcription factor activity term: id: GO:0003700 label: DNA-binding transcription factor activity gene_product: preferred_term: cII (Escherichia phage lambda) term: id: UniProtKB:P03042 label: Transcriptional activator II description: Lambdoid CII transcription activator (stabilized by CIII inhibition of host FtsH protease) that activates CI repressor and Int integrase transcription. function: preferred_term: DNA-binding transcription factor activity term: id: GO:0003700 label: DNA-binding transcription factor activity processes: - preferred_term: latency-replication decision term: id: GO:0098689 label: latency-replication decision - preferred_term: establishment of viral latency term: id: GO:0019043 label: establishment of viral latency locations: - preferred_term: host cell cytoplasm term: id: GO:0030430 label: host cell cytoplasm role_description: Integrates MOI and host protease status to activate transcription of the lysogenic repressor and integrase. - order: 2 role: CI-Cro bistable operator maintenance and SOS induction node: id: ci_cro_bistable_maintenance label: CI repressor maintenance of latency and RecA-stimulated induction module_type: BIOLOGICAL_PROCESS annotons: - id: ci_repressor_maintenance label: CI master repressor operator binding and SOS autocleavage participant: selector_type: ANY_WITH_FUNCTION required_function: preferred_term: DNA-binding transcription factor activity term: id: GO:0003700 label: DNA-binding transcription factor activity gene_product: preferred_term: cI (Escherichia phage lambda) term: id: UniProtKB:P03034 label: Repressor protein cI description: Master lysogenic repressor CI (and competing lytic repressor Cro) binding oR/oL operators to maintain viral latency until host SOS-activated RecA* stimulates CI autoproteolysis (`GO:0019046`). function: preferred_term: DNA-binding transcription factor activity term: id: GO:0003700 label: DNA-binding transcription factor activity processes: - preferred_term: latency-replication decision term: id: GO:0098689 label: latency-replication decision - preferred_term: maintenance of viral latency term: id: GO:0019044 label: maintenance of viral latency - preferred_term: release from viral latency term: id: GO:0019046 label: release from viral latency locations: - preferred_term: host cell cytoplasm term: id: GO:0030430 label: host cell cytoplasm role_description: Silences lytic promoters during prophage maintenance and undergoes RecA*-stimulated cleavage upon host DNA damage to trigger prophage induction. connections: - source: cii_ciii_latency_commitment target: ci_cro_bistable_maintenance connection_type: POSITIVELY_REGULATES predicate: preferred_term: positively regulates term: id: RO:0002213 label: positively regulates description: CII activates initial CI synthesis from the pRE promoter, enabling CI to occupy oR1/oR2 and establish self-sustaining maintenance from pRM. - id: arbitrium_peptide_quorum_switch label: Arbitrium peptide quorum-sensing lysis-lysogeny switch (SPbeta/phi3T-type) module_type: BIOLOGICAL_PROCESS description: Bacillus phages encode a secreted hexapeptide signal (AimP) that is imported into neighboring bacteria via Opp oligopeptide permease and bound by the intracellular receptor transcription factor AimR, inhibiting AimX expression to promote lysogeny at high phage population density. annotons: - id: aimp_aimr_arbitrium_signaling label: Arbitrium AimP-AimR peptide-regulated latency decision participant: selector_type: ANY_WITH_FUNCTION required_function: preferred_term: DNA-binding transcription factor activity term: id: GO:0003700 label: DNA-binding transcription factor activity description: Arbitrium peptide receptor transcription factor AimR and signaling peptide AimP in SPbeta-group Bacillus phages. function: preferred_term: DNA-binding transcription factor activity term: id: GO:0003700 label: DNA-binding transcription factor activity processes: - preferred_term: latency-replication decision term: id: GO:0098689 label: latency-replication decision locations: - preferred_term: host cell cytoplasm term: id: GO:0030430 label: host cell cytoplasm evidence: - source_id: PMID:28099413 statement: Phage-encoded arbitrium peptides and AimR receptors regulate the lysis-lysogeny decision. supporting_text: Here we show that viruses (phages) of the SPbeta group use a small-molecule communication system to coordinate lysis-lysogeny decisions. role_description: Senses extracellular arbitrium peptide accumulation to switch infected cells from lytic replication to lysogeny. - id: prophage_persistence_and_excision_mode label: Prophage genome persistence and excision mechanism axis: site-specific chromosomal integration vs. extrachromosomal episomal maintenance vs. replicative transposition integration selection: EXACTLY_ONE notes: Once committed to latency, temperate phages maintain their prophage genome either integrated at an att site via a tyrosine/serine integrase, as an extrachromosomal circular/linear plasmid replicon, or integrated across host chromosome sites via a DDE transposase. variants: - id: site_specific_integrated_prophage label: Site-specific chromosomal integration and excisionase-directed excision (lambda/P22/P2-type) module_type: BIOLOGICAL_PROCESS description: A phage-encoded tyrosine or serine site-specific integrase (`Int`, `GO:0008979`) catalyzes recombination between phage `attP` and host `attB` (`GO:0075713`), assisted by host IHF; upon induction, excisionase (`Xis` or `Cox`) bends DNA to direct integrase-catalyzed excisive recombination (`attL` x `attR`, `GO:0032359`). annotons: - id: prophage_integrase_and_excisionase label: Prophage site-specific integration and Xis-directed excision participant: selector_type: ANY_WITH_FUNCTION required_function: preferred_term: prophage integrase activity term: id: GO:0008979 label: prophage integrase activity gene_product: preferred_term: int (Escherichia phage lambda) term: id: UniProtKB:P03700 label: Integrase description: Temperate phage tyrosine/serine integrase (lambda Int, P2 Int, P4 Int) and directionality factor/excisionase (lambda Xis, P2 Cox). function: preferred_term: prophage integrase activity term: id: GO:0008979 label: prophage integrase activity processes: - preferred_term: establishment of integrated proviral latency term: id: GO:0075713 label: establishment of integrated proviral latency - preferred_term: provirus excision term: id: GO:0032359 label: provirus excision locations: - preferred_term: host cell cytoplasm term: id: GO:0030430 label: host cell cytoplasm role_description: Catalyzes site-specific integration of the phage genome into the host chromosome and Xis-dependent excision upon induction. - id: episomal_plasmid_prophage label: Extrachromosomal circular or linear telomeric plasmid prophage (P1/N15-type) module_type: BIOLOGICAL_PROCESS description: Temperate phages such as P1 (circular plasmid prophage maintained by RepA and partitioned by ParA/ParB, `GO:0075720`) and N15 (linear plasmid prophage with hairpin telomeres generated by protelomerase TelN, `GO:0075530`) persist extrachromosomally during latency without integrating into the host chromosome. annotons: - id: episomal_prophage_maintenance label: Episomal circular or linear plasmid prophage maintenance participant: selector_type: ANY_PARTICIPANT gene_product: preferred_term: parA (Escherichia phage P1) term: id: UniProtKB:P07620 label: Plasmid partition protein A description: Plasmid prophage replication/partition proteins (P1 RepA, ParA, ParB; N15 TelN protelomerase and RepA) that maintain extrachromosomal viral latency. function: preferred_term: DNA binding term: id: GO:0003677 label: DNA binding processes: - preferred_term: establishment of episomal latency term: id: GO:0075720 label: establishment of episomal latency - preferred_term: establishment of latency as a linear episome term: id: GO:0075530 label: establishment of latency as a linear episome - preferred_term: maintenance of viral latency term: id: GO:0019044 label: maintenance of viral latency locations: - preferred_term: host cell cytoplasm term: id: GO:0030430 label: host cell cytoplasm role_description: Establishes and partitions an extrachromosomal circular or linear prophage replicon during host cell division. - id: transposable_prophage_integration label: Replicative transposition prophage integration and maintenance (Mu-type) module_type: BIOLOGICAL_PROCESS description: Transposable temperate phages (such as Escherichia phage Mu and Pseudomonas phage D3112) use a DDE-family transposase (`MuA`, `GO:0004803`) and ATP-dependent target-site immunity protein (`MuB`) to integrate randomly into the host chromosome (`GO:0075713`, `GO:0015074`) and amplify via replicative transposition upon prophage induction without excising a circular genome. annotons: - id: mu_transposase_integration label: Transposase-mediated proviral chromosomal integration participant: selector_type: ANY_WITH_FUNCTION required_function: preferred_term: transposase activity term: id: GO:0004803 label: transposase activity gene_product: preferred_term: A (Escherichia phage Mu) term: id: UniProtKB:P07636 label: DDE-recombinase A description: Phage-encoded DDE transposase (such as Mu gpA) and transposition regulator (Mu gpB) catalyzing non-site-specific chromosomal integration and replicative transposition. function: preferred_term: transposase activity term: id: GO:0004803 label: transposase activity processes: - preferred_term: establishment of integrated proviral latency term: id: GO:0075713 label: establishment of integrated proviral latency - preferred_term: DNA integration term: id: GO:0015074 label: DNA integration locations: - preferred_term: host cell cytoplasm term: id: GO:0030430 label: host cell cytoplasm role_description: Integrates the phage genome into random host chromosomal target sites and drives replicative transposition during lytic induction. knowledge_gaps: - gap_statement: Gene Ontology uses the general viral terms "viral latency" (GO:0019042) and "release from viral latency" (GO:0019046) without exact synonyms or bacteriophage-specific terms for "lysogeny" and "prophage induction". Biologically, the environmental triggers and host signaling pathways governing non-SOS prophage induction and phage-encoded quorum-sensing circuits remain unknown for the majority of temperate phages. boundary: Map all temperate phage lysogeny and prophage induction annotations to the GO:0019042 / GO:0098689 / GO:0019046 latency hierarchy. gap_kind: - BIOLOGY - ONTOLOGY