prophage

Deep research

Generated by just research-trait; source: research/traits/genomics/prophage-deep-research-falcon.md

# Curation report: prophage (`traitmech:000091`)

## Executive summary

The reviewed class should represent **possession and lysogenic maintenance of a temperate bacteriophage genome**, ordinarily integrated into the bacterial chromosome but sometimes maintained as a low-copy extrachromosomal replicon. The core causal graph should terminate at the stable lysogenic state: site-specific integration or episomal maintenance, repression of lytic genes, vertical inheritance, and the resulting prophage-positive cell. Induction and host phenotypes are important downstream or contextual branches, not necessary defining conditions.

Recent work substantially refines this picture. A 2023 *Staphylococcus aureus* study showed that SOS-mediated CI cleavage is not necessarily sufficient for induction: ClpX must inactivate the residual DNA-binding CI N-terminal fragment, and loss of ClpX reduced spontaneous prophage release by more than two orders of magnitude. This is a strong but taxon/model-specific extension of the classical RecA–CI switch (thabet2023theclpxprotease pages 6-8, thabet2023theclpxprotease pages 11-12, thabet2023theclpxprotease pages 10-11). Large 2024 surveys also demonstrate that prevalence and completeness are strongly dataset- and taxon-dependent: 105,613 predicted regions occurred in approximately 92% of 43,942 human-gut bacterial genomes, whereas prophages occurred in 29.5% of 1,011 closed *Helicobacter pylori* genomes and only 32.2% of prophage-positive *H. pylori* genomes contained a complete prophage (pei2024auniverseof pages 1-2, vale2024genecontentphage pages 1-2).

## 1. Scope and boundaries

### Recommended scope

**Trait label:** prophage  
**Identifier:** `traitmech:000091`  
**Category:** GENOMICS  
**Term kind:** CLASS  
**Parent:** `traitmech:000089`  
**Synonym:** lysogen

Recommended operational definition:

> A genomic trait in which a microbial cell possesses a temperate-phage genome maintained during lysogeny, usually by chromosomal integration and vertical inheritance, but potentially as a stably maintained low-copy extrachromosomal replicon. Most lytic-cycle genes are transcriptionally repressed; element-specific accessory genes may remain expressed and alter host phenotype.

Temperate phages become prophages by entering lysogeny and are inherited with the host genome. Stable persistence requires repression because virion-production and lysis genes are toxic to the bacterial host; in the lambda paradigm, CI alone can maintain lysogeny (vale2024genecontentphage pages 1-2, owen2020awindowinto pages 1-2). The class therefore denotes **element carriage/state**, not a universal physiological outcome such as virulence, resistance, biofilm formation, or inducibility.

### Boundary cases

1. **Free lytic infection:** exclude. A lytic phage immediately proceeds through genome replication, packaging, progeny production, and host lysis; it is not a prophage-positive lysogen (vale2024genecontentphage pages 1-2).
2. **Induced prophage:** retain as a downstream transition from the trait, but do not equate it with the trait itself. Induction ends stable lysogenic repression and initiates productive development.
3. **Defective or cryptic prophage:** annotate with a qualifier or child state. Such remnants can no longer complete excision, particle production, lysis, or infectivity, yet may retain functional host-modifying genes. Most prophages show some degree of defect or decay, and *H. pylori* decay involves rearrangement, pseudogene accumulation, deletion, and merger with other mobile elements (bobay2014pervasivedomesticationof pages 1-2, vale2024genecontentphage pages 1-2).
4. **Prophage-like genomic region predicted in silico:** evidence for the trait, not definitive proof. Completeness and activity require intact boundaries/modules or experimental induction.
5. **Phage-inducible chromosomal islands and other satellites:** exclude from the class unless a bona fide temperate-phage genome is independently present. Satellites require a helper phage, although they also encode integrases and use att sites. A 2023 study observed composite excision, replication, and later satellite excision and mapped 491 helper-embedded PICIs, illustrating why automated tools can confuse nested satellites with prophage sequence (tommasini2023helperembeddedsatellitesfrom pages 1-2).
6. **Gene-transfer agents, plasmids, ICEs, and other genomic islands:** exclude unless evidence establishes a temperate-phage genome. Integrase and attachment sites alone are not specific.
7. **“Lysogen”:** properly denotes the host cell carrying a prophage, rather than the phage DNA itself.

## 2. Candidate nodes

### Trait and element-state nodes

- `traitmech:000091` — prophage
- temperate bacteriophage genome — label-only candidate
- integrated prophage genome — label-only candidate
- extrachromosomal prophage/episomal temperate-phage genome — label-only candidate
- lysogen / prophage-positive host cell — label-only candidate
- complete, inducible prophage — label-only candidate
- defective/cryptic prophage — label-only candidate
- prophage remnant — label-only candidate
- prophage induction; lysogenic-to-lytic transition — label-only unless a suitable ontology term is verified

### Genes, proteins, and molecular complexes

- **Phage integrase (Int):** site-specific recombinase acting at attachment sites. Use the applicable protein-family or gene identifier for the actual phage; do not assign one universal UniProt identifier.
- **Attachment sites:** attP, attB, attL, attR; sequence features rather than genes.
- **CI-like master repressor:** maintains repression of lytic transcription. CI is not universal across all temperate phages, so use a family/model-specific label.
- **Cro/antirepressor:** candidate switch regulators; include only where demonstrated for the selected system.
- **RecA:** activated RecA nucleoprotein state (`RecA*`) promotes autocleavage of susceptible repressors. Gene/protein identifiers should be taxon-specific.
- **LexA:** bacterial SOS repressor; useful upstream of induction but not a prophage component.
- **ClpX and ClpP:** host ATP-dependent protease machinery. The demonstrated ClpX–CI mechanism is specific to *S. aureus* Φ11/80α; ClpP acts upstream in the staphylococcal SOS response (thabet2023theclpxprotease pages 3-4, thabet2023theclpxprotease pages 11-12).
- **Excisionase/recombination directionality factor (Xis/RDF; sometimes AlpA-like):** redirects integrase-mediated recombination toward excision.
- **Terminase, portal, capsid, tail, holin, endolysin:** useful completeness and productive-cycle markers, but not required to define a decayed prophage. In one large survey, only 43% of predictions had an annotated integrase and 45.7% of predicted prophage ORFs lacked functional annotation (kang2017prophagegenomicsreveals pages 4-7).

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