Panoptes system

traitmech:000407 · CLASS · PROPOSED

A phage defense system in which an organism possesses a two-gene optSE locus encoding an OptS protein that constitutively produces cyclic dinucleotides and an OptE transmembrane effector that is released from cyclic-dinucleotide repression when phage Acb2-like proteins sequester those signals, leading to inner-membrane disruption.

Trait evidence (8)

DOI:10.1038/s41586-025-09557-z
Panoptes is a two-gene operon, optSE, wherein OptS is predicted to synthesize a nucleotide-derived second messenger and OptE is predicted to bind that signal and drive effector-mediated defence.

Sullivan et al. define Panoptes as the two-gene optSE system encoding OptS and OptE.
DOI:10.1038/s41586-025-09557-z
We named OptSE the Panoptes antiphage system for Argus Panoptes, the all-seeing, many-eyed giant in Greek mythology who was a faithful watchman to Hera.

Sullivan et al. name OptSE as the Panoptes antiphage system.
DOI:10.1038/s41586-025-09557-z
OptS orthologues from two distinct Panoptes systems generated cyclic dinucleotide products, including 2′,3′-cyclic diadenosine monophosphate (2′,3′-c-di-AMP), which we showed were able to bind the soluble domain of the OptE transmembrane effector.

OptS orthologues produce cyclic dinucleotides, including 2′,3′-c-di-AMP, that can bind the soluble domain of the OptE transmembrane effector.
DOI:10.1038/s41586-025-09557-z
Panoptes potently restricted phage replication, but phages that had loss-of-function mutations in anti-cyclic oligonucleotide-based antiphage signalling system (CBASS) protein 2 (Acb2) escaped defence.

Phage replication was restricted by Panoptes, while Acb2 loss-of-function mutations escaped defense.
DOI:10.1038/s41586-025-09557-z
Our data support the idea that cyclic nucleotide sequestration by Acb2 releases OptE toxicity, thereby initiating inner membrane disruption, leading to phage defence.

Acb2 cyclic-nucleotide sequestration releases OptE toxicity and leads to inner-membrane disruption.
DOI:10.1038/s41586-025-09557-z
We investigated a candidate two-gene Panoptes operon from Vibrio navarrensis.

Sullivan et al. used a Vibrio navarrensis optSE locus for direct Panoptes defense assays.
DOI:10.1038/s41586-025-09557-z
We expressed the operon from its endogenous promoter in Escherichia coli MG1655 and challenged these bacteria with a panel of diverse phages. The VnOptSE operon specifically defended against phages from the Straboviridae family

The V. navarrensis operon was expressed from its endogenous promoter in E. coli MG1655 and protected the heterologous host against Straboviridae phages.
https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
| Panoptes | 10\.1038/s41586-025-09557-z | The Panoptes system uses decoy cyclic nucleotides to defend against phage |

The pinned DefenseFinder article registry maps the Panoptes key to Sullivan et al.; the same pinned rules and HMM inventory omit a Panoptes model.

Panoptes loci couple cyclic-nucleotide sequestration to OptE membrane disruption

Evidence-backed process sketch linking an optSE locus to OptS cyclic-dinucleotide synthesis, OptE repression, Acb2-like sequestration of the OptS-derived signal, inner-membrane disruption, and phage restriction.

MECHANISTIC · The graph captures OptS/OptE/Acb2 coupling from Sullivan et al. while leaving cyclic-dinucleotide identity, anti-defense breadth, phage breadth, and OptE oligomerization unspecified for untested optSE homologs.

Edge evidence

optSE locus encodes OptS cyclic-dinucleotide synthase
Panoptes optSE loci encode OptS cyclic-dinucleotide synthases.
- DOI:10.1038/s41586-025-09557-z Panoptes is a two-gene operon, optSE, wherein OptS is predicted to synthesize a nucleotide-derived second messenger and OptE is predicted to bind that signal and drive effector-mediated defence. Sullivan et al. define Panoptes as the two-gene optSE system encoding OptS and OptE.
- DOI:10.1038/s41586-025-09557-z We investigated a candidate two-gene Panoptes operon from Vibrio navarrensis. Sullivan et al. used a Vibrio navarrensis optSE locus for direct Panoptes defense assays.
optSE locus encodes OptE transmembrane effector
Panoptes optSE loci encode OptE transmembrane effectors.
- DOI:10.1038/s41586-025-09557-z Panoptes is a two-gene operon, optSE, wherein OptS is predicted to synthesize a nucleotide-derived second messenger and OptE is predicted to bind that signal and drive effector-mediated defence. Sullivan et al. define Panoptes as the two-gene optSE system encoding OptS and OptE.
- DOI:10.1038/s41586-025-09557-z We investigated a candidate two-gene Panoptes operon from Vibrio navarrensis. Sullivan et al. used a Vibrio navarrensis optSE locus for direct Panoptes defense assays.
OptS cyclic-dinucleotide synthase contributes to OptS cyclic dinucleotide synthesis RO:0002326
OptS is the Panoptes synthase that generates OptE-binding cyclic dinucleotides.
- DOI:10.1038/s41586-025-09557-z OptS orthologues from two distinct Panoptes systems generated cyclic dinucleotide products, including 2′,3′-cyclic diadenosine monophosphate (2′,3′-c-di-AMP), which we showed were able to bind the soluble domain of the OptE transmembrane effector. OptS orthologues produce cyclic dinucleotides, including 2′,3′-c-di-AMP, that can bind the soluble domain of the OptE transmembrane effector.
OptS cyclic dinucleotide synthesis contributes to OptE cyclic dinucleotide repression RO:0002326
OptS-derived cyclic dinucleotides bind OptE and hold the effector in an inactive state before phage counter-defense challenge.
- DOI:10.1038/s41586-025-09557-z OptS orthologues from two distinct Panoptes systems generated cyclic dinucleotide products, including 2′,3′-cyclic diadenosine monophosphate (2′,3′-c-di-AMP), which we showed were able to bind the soluble domain of the OptE transmembrane effector. OptS orthologues produce cyclic dinucleotides, including 2′,3′-c-di-AMP, that can bind the soluble domain of the OptE transmembrane effector.
- DOI:10.1038/s41586-025-09557-z we found that OptS constitutively produced signalling nucleotides to repress OptE-mediated growth inhibition. OptS constitutive signalling nucleotide production represses OptE-mediated growth inhibition.
OptE cyclic dinucleotide repression negatively regulates OptE inner membrane disruption RO:0002212
Cyclic-dinucleotide binding restrains OptE-mediated toxicity and inner-membrane disruption.
- DOI:10.1038/s41586-025-09557-z we found that OptS constitutively produced signalling nucleotides to repress OptE-mediated growth inhibition. OptS constitutive signalling nucleotide production represses OptE-mediated growth inhibition.
OptE transmembrane effector contributes to OptE inner membrane disruption RO:0002326
OptE is the Panoptes effector whose released toxicity disrupts the inner membrane.
- DOI:10.1038/s41586-025-09557-z Our data support the idea that cyclic nucleotide sequestration by Acb2 releases OptE toxicity, thereby initiating inner membrane disruption, leading to phage defence. Acb2 cyclic-nucleotide sequestration releases OptE toxicity and leads to inner-membrane disruption.
phage infection activates Acb2-like signal sequestration RO:0002213
Phage infection produces Acb2 or similar immune-evasion proteins that sequester OptS-derived cyclic nucleotide signals.
- DOI:10.1038/s41586-025-09557-z During phage infection, Acb2 or similar immune evasion proteins are produced that sequester the OptS-derived signalling molecule, leading to a population of OptE that is no longer bound to cyclic dinucleotide and is free to become activated, in turn disrupting the bacterial membrane and resulting in phage defence The Panoptes model links Acb2-like signal sequestration to OptE activation, bacterial membrane disruption, and phage defense.
Acb2-like signal sequestration activates OptE inner membrane disruption RO:0002213
Acb2 or similar immune-evasion proteins sequester the OptS-derived signal and release OptE-mediated membrane disruption.
- DOI:10.1038/s41586-025-09557-z Our data support the idea that cyclic nucleotide sequestration by Acb2 releases OptE toxicity, thereby initiating inner membrane disruption, leading to phage defence. Acb2 cyclic-nucleotide sequestration releases OptE toxicity and leads to inner-membrane disruption.
OptE inner membrane disruption mitigates phage replication METPO:2007407
Panoptes-associated OptE membrane disruption restricts bacteriophage replication.
- DOI:10.1038/s41586-025-09557-z Panoptes potently restricted phage replication, but phages that had loss-of-function mutations in anti-cyclic oligonucleotide-based antiphage signalling system (CBASS) protein 2 (Acb2) escaped defence. Phage replication was restricted by Panoptes, while Acb2 loss-of-function mutations escaped defense.
OptE inner membrane disruption confers Panoptes system METPO:2007700
OptE-mediated inner-membrane disruption is the phage-defense output that realizes the Panoptes system trait.
- DOI:10.1038/s41586-025-09557-z During phage infection, Acb2 or similar immune evasion proteins are produced that sequester the OptS-derived signalling molecule, leading to a population of OptE that is no longer bound to cyclic dinucleotide and is free to become activated, in turn disrupting the bacterial membrane and resulting in phage defence The Panoptes model links Acb2-like signal sequestration to OptE activation, bacterial membrane disruption, and phage defense.
Panoptes system is a phage defense system rdfs:subClassOf
Panoptes system possession is a phage-defense-system trait.
- DOI:10.1038/s41586-025-09557-z We named OptSE the Panoptes antiphage system for Argus Panoptes, the all-seeing, many-eyed giant in Greek mythology who was a faithful watchman to Hera. Sullivan et al. name OptSE as the Panoptes antiphage system.

Protein and taxon examples

Graph node Protein Taxon UniProt status Role and evidence

OptS cyclic-dinucleotide synthase

Graph node	Protein	Taxon	UniProt status	Role and evidence
OptS cyclic-dinucleotide synthase	`UniProtKB:A0A099LXT1` Minimal CRISPR polymerase domain-containing protein (optS)	Vibrio navarrensis `NCBITaxon:29495`	`UNREVIEWED` retrieved 2026-09-27 · entry v30 · sequence v1	VnOptS is the OptS synthase encoded by the V. navarrensis optSE Panoptes operon. `DOI:10.1038/s41586-025-09557-z` We investigated a candidate two-gene Panoptes operon from Vibrio navarrensis. Sullivan et al. used a Vibrio navarrensis optSE locus for direct Panoptes defense assays. `DOI:10.1038/s41586-025-09557-z` OptS orthologues from two distinct Panoptes systems generated cyclic dinucleotide products, including 2′,3′-cyclic diadenosine monophosphate (2′,3′-c-di-AMP), which we showed were able to bind the soluble domain of the OptE transmembrane effector. OptS orthologues produce cyclic dinucleotides, including 2′,3′-c-di-AMP, that can bind the soluble domain of the OptE transmembrane effector.
OptE transmembrane effector	`UniProtKB:A0A099LW44` CD-NTase-associated protein 15 domain-containing protein (optE)	Vibrio navarrensis `NCBITaxon:29495`	`UNREVIEWED` retrieved 2026-09-27 · entry v37 · sequence v1	VnOptE is the OptE transmembrane effector encoded by the V. navarrensis optSE Panoptes operon. `DOI:10.1038/s41586-025-09557-z` Panoptes is a two-gene operon, optSE, wherein OptS is predicted to synthesize a nucleotide-derived second messenger and OptE is predicted to bind that signal and drive effector-mediated defence. Sullivan et al. define Panoptes as the two-gene optSE system encoding OptS and OptE. `DOI:10.1038/s41586-025-09557-z` OptS orthologues from two distinct Panoptes systems generated cyclic dinucleotide products, including 2′,3′-cyclic diadenosine monophosphate (2′,3′-c-di-AMP), which we showed were able to bind the soluble domain of the OptE transmembrane effector. OptS orthologues produce cyclic dinucleotides, including 2′,3′-c-di-AMP, that can bind the soluble domain of the OptE transmembrane effector. `DOI:10.1038/s41586-025-09557-z` We expressed the operon from its endogenous promoter in Escherichia coli MG1655 and challenged these bacteria with a panel of diverse phages. The VnOptSE operon specifically defended against phages from the Straboviridae family The V. navarrensis operon was expressed from its endogenous promoter in E. coli MG1655 and protected the heterologous host against Straboviridae phages.

UniProtKB:A0A099LXT1
Minimal CRISPR polymerase domain-containing protein (optS)

Vibrio navarrensis
NCBITaxon:29495

UNREVIEWED
retrieved 2026-09-27 · entry v30 · sequence v1

VnOptS is the OptS synthase encoded by the V. navarrensis optSE Panoptes operon.

DOI:10.1038/s41586-025-09557-z We investigated a candidate two-gene Panoptes operon from Vibrio navarrensis. Sullivan et al. used a Vibrio navarrensis optSE locus for direct Panoptes defense assays.
DOI:10.1038/s41586-025-09557-z OptS orthologues from two distinct Panoptes systems generated cyclic dinucleotide products, including 2′,3′-cyclic diadenosine monophosphate (2′,3′-c-di-AMP), which we showed were able to bind the soluble domain of the OptE transmembrane effector. OptS orthologues produce cyclic dinucleotides, including 2′,3′-c-di-AMP, that can bind the soluble domain of the OptE transmembrane effector.

OptE transmembrane effector

UniProtKB:A0A099LW44
CD-NTase-associated protein 15 domain-containing protein (optE)

Vibrio navarrensis
NCBITaxon:29495

UNREVIEWED
retrieved 2026-09-27 · entry v37 · sequence v1

VnOptE is the OptE transmembrane effector encoded by the V. navarrensis optSE Panoptes operon.

DOI:10.1038/s41586-025-09557-z Panoptes is a two-gene operon, optSE, wherein OptS is predicted to synthesize a nucleotide-derived second messenger and OptE is predicted to bind that signal and drive effector-mediated defence. Sullivan et al. define Panoptes as the two-gene optSE system encoding OptS and OptE.
DOI:10.1038/s41586-025-09557-z OptS orthologues from two distinct Panoptes systems generated cyclic dinucleotide products, including 2′,3′-cyclic diadenosine monophosphate (2′,3′-c-di-AMP), which we showed were able to bind the soluble domain of the OptE transmembrane effector. OptS orthologues produce cyclic dinucleotides, including 2′,3′-c-di-AMP, that can bind the soluble domain of the OptE transmembrane effector.
DOI:10.1038/s41586-025-09557-z We expressed the operon from its endogenous promoter in Escherichia coli MG1655 and challenged these bacteria with a panel of diverse phages. The VnOptSE operon specifically defended against phages from the Straboviridae family The V. navarrensis operon was expressed from its endogenous promoter in E. coli MG1655 and protected the heterologous host against Straboviridae phages.

Provenance

Identifier source: TraitMech local identifier
Definition source: DOI:10.1038/s41586-025-09557-z

Parent traits (1)

phage defense system traitmech:000209

Synonyms (3)

Panoptes antiphage system EXACT_SYNONYM · DOI:10.1038/s41586-025-09557-z
optSE RELATED_SYNONYM · DOI:10.1038/s41586-025-09557-z
OptSE RELATED_SYNONYM · DOI:10.1038/s41586-025-09557-z

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.

Vibrio navarrensis NCBITaxon:29495 DOI:10.1038/s41586-025-09557-z Species carrying the assayed VnOptSE Panoptes system; defense activity was tested heterologously from the endogenous V. navarrensis promoter in E. coli MG1655.

Discussions and Knowledge Gaps (2)

Open questions attached to this trait. Seeded by just knowledge-gap-scan and curated; see the corpus-wide index.

Recheck DefenseFinder Panoptes rules and HMM profiles before using DefenseFinder model rows as optSE profile evidence.

CURATION TODO OPEN panoptes-defensefinder-model-gap · raised by codex · 2026-09-27

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.

The pinned DefenseFinder article registry maps Panoptes to Sullivan et al. and the Nature article title, but the pinned DefenseFinder rules and HMM inventories do not include Panoptes rows. This record therefore cites the DOI-backed article and treats the article registry as name-to-paper evidence rather than as profile support.

Evidence

https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
| Panoptes | 10\.1038/s41586-025-09557-z | The Panoptes system uses decoy cyclic nucleotides to defend against phage |

Find a native endogenous microbial isolate with direct chromosomal Panoptes antiphage validation beyond the heterologous VnOptSE source-species exemplar.

KNOWLEDGE GAP OPEN panoptes-natural-host-gap · raised by codex · 2026-09-27

Attached to causal_graphs#panoptes_decoy_cyclic_nucleotide_defense

Sullivan et al. investigated a candidate Vibrio navarrensis optSE operon and showed that VnOptSE defended against Straboviridae phages when expressed in E. coli MG1655 from its endogenous promoter. V. navarrensis is retained as the operon source for mechanistic protein examples, but that heterologous challenge assay does not establish a direct endogenous V. navarrensis chromosomal Panoptes assay.

Evidence

DOI:10.1038/s41586-025-09557-z
We investigated a candidate two-gene Panoptes operon from Vibrio navarrensis.
DOI:10.1038/s41586-025-09557-z
We expressed the operon from its endogenous promoter in Escherichia coli MG1655 and challenged these bacteria with a panel of diverse phages. The VnOptSE operon specifically defended against phages from the Straboviridae family

Curation history

2026-09-27T09:24:21Z · MINTED_TRAITMECH_ID · codex
Minted Panoptes system as a DOI-backed GENOMICS TraitRecord under phage defense system after an ignored-and-hidden duplicate review found no exact live TraitMech, METPO, history, or prior proposal record; the replacement placeholder is reserved in proposals/metpo_traitmech_v284.
2026-09-27T09:24:22Z · REVIEW_CANONICAL_EXAMPLE_EVIDENCE_GAP · codex
Reviewed Panoptes system canonical_examples and added V. navarrensis as the VnOptSE operon source for the mechanistic protein examples; direct native chromosomal Panoptes activity remains open because the current challenge assay used heterologous E. coli MG1655. No paid research was used.
2026-09-27T11:38:27Z · VERIFY_PANOPTES_PROTEIN_GROUNDINGS · codex
Verified the Panoptes UniProt protein examples with audit_uniprot_grounding.py: UniProtKB:A0A099LXT1 is a current unreviewed V. navarrensis UP000029994 primary accession at entry version 30 / sequence version 1, UniProtKB:A0A099LW44 is a current unreviewed V. navarrensis UP000029994 primary accession at entry version 37 / sequence version 1, and UniProt cross-references link them to InterPro:IPR040942 (Minimal_Cpol) and InterPro:IPR041208 (Cap15).
2026-09-27T11:59:19Z · DOCUMENT_PANOPTES_INTERPRO_SCOPE · codex
Added grounding notes for the new Panoptes InterPro CURIEs: InterPro:IPR040942 is a broader Minimal_Cpol domain present in VnOptS rather than an OptS-only family, and InterPro:IPR041208 is the Cap15 family carried by VnOptE.