{
  "abstract": "Cyclic nucleotide second messengers are used in all domains of life to amplify viral infection signals and activate cellular defences. In prokaryotes, CBASS (cyclic nucleotide-based antiphage signalling system) and type III CRISPR-Cas systems generate a range of cyclic nucleotides which bind and allosterically activate effector proteins to mount an anti-viral response. Viruses have evolved counter measures to antagonise these signalling pathways in the form of cyclic nucleotide sponges and phosphodiesterases that sequester or degrade these molecules to subvert immunity. Recently, the Panoptes system was shown to function as a guard against these viral tactics. The type I Panoptes polymerase, mCpol, generates cyclic dinucleotides as decoy molecules that, when sequestered by phage proteins, results in the activation of the membrane-permeabilising effector 2TMβ to halt the phage infection cycle. Here, we investigate the type II Panoptes system, demonstrating that it generates cyclic tri-adenylate (cA3) to maintain a CRISPR-associated Rossmann fold-transmembrane (CARF-TM) effector in an inactive, dimeric state. When cA3 is sequestered or degraded, the CARF protein undergoes conformational changes. In vivo, the absence of cA3 results in membrane disruption and growth arrest. Type II Panoptes provides defence against phages that express the cA3-degrading enzyme Acb1; phage escapers introduce mutations into the acb1 gene to avoid triggering the Panoptes system. These findings expand our understanding of the guard systems that constitute a fascinating component of the bacterial immune system.\n\nPhages can evade bacterial immunity by disrupting antiviral signals such as cyclic tri-adenylate (cA3), triggering the Panoptes defense systems. This study shows that Type II Panoptes detects cA3 loss and activates a CARF-TM effector to disrupt membranes and stop infection.",
  "abstract_shown": true,
  "affiliations": [
    "University of St Andrews"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Sabine Grüschow"
    },
    {
      "affs": [
        0
      ],
      "name": "Peter J. Wotherspoon",
      "orcid": "0000-0002-4973-2830"
    },
    {
      "affs": [
        0
      ],
      "name": "Emma Hilton-Balfe"
    },
    {
      "affs": [
        0
      ],
      "name": "Shirley Graham",
      "orcid": "0000-0002-2608-3815"
    },
    {
      "affs": [
        0
      ],
      "name": "Malcolm F. White",
      "orcid": "0000-0003-1543-9342"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dn4ap54whtyjm.bib",
  "cited_by": 5,
  "doi": "10.1371/journal.pbio.3003934",
  "fulltext_url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003934",
  "id": "dn4ap54whtyjm",
  "issns": [
    "1545-7885",
    "1544-9173"
  ],
  "landing_url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003934",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2303|Bacteriophages and microbial interactions"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Enzymology/Enzymes/Hydrolases/Nucleases"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Nucleotides"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/DNA-binding proteins/Nucleases"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Enzymes/Hydrolases/Nucleases"
    ],
    [
      "plos",
      "/Biology and life sciences/Bioengineering/Genome engineering/Synthetic genome editing/CRISPR"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Medical microbiology/Microbial pathogens/Bacterial pathogens/Escherichia coli"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Bacteria/Enterobacteriaceae/Escherichia/Escherichia coli"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Bacteria/Gut bacteria/Escherichia/Escherichia coli"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Viruses/Bacteriophages"
    ],
    [
      "plos",
      "/Biology and life sciences/Synthetic biology/Synthetic genomics/Synthetic genome editing/CRISPR"
    ],
    [
      "plos",
      "/Engineering and technology/Bioengineering/Genome engineering/Synthetic genome editing/CRISPR"
    ],
    [
      "plos",
      "/Engineering and technology/Synthetic biology/Synthetic genomics/Synthetic genome editing/CRISPR"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Microbial pathogens/Bacterial pathogens/Escherichia coli"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Polymer chemistry/Dimers"
    ],
    [
      "plos",
      "/Physical sciences/Materials science/Materials/Oligomers/Dimers"
    ],
    [
      "plos",
      "/Research and analysis methods/Animal studies/Experimental organism systems/Model organisms/Escherichia coli"
    ],
    [
      "plos",
      "/Research and analysis methods/Animal studies/Experimental organism systems/Prokaryotic models/Escherichia coli"
    ],
    [
      "plos",
      "/Research and analysis methods/Model organisms/Escherichia coli"
    ],
    [
      "plos",
      "/Research and analysis methods/Specimen preparation and treatment/Staining/Cell staining"
    ],
    [
      "plos",
      "/Research and analysis methods/Specimen preparation and treatment/Staining/Membrane staining"
    ]
  ],
  "openalex": "W7213273537",
  "pdf_url": "https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3003934&type=printable",
  "pmcid": "PMC13577387",
  "pmid": "42743106",
  "published": "2026-09-15",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/dn4ap54whtyjm.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:49Z",
      "native_id": "10.1371/journal.pbio.3003934",
      "source": "plos",
      "url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003934"
    },
    {
      "first_seen": "2026-11-04T13:21:18Z",
      "native_id": "W7213273537",
      "source": "openalex",
      "url": "https://doi.org/10.1371/journal.pbio.3003934"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "plos:bioengineering",
      "subfield": "systems-synthetic"
    },
    {
      "field": "chemistry",
      "origin": "plos:polymer chemistry",
      "subfield": "materials-polymers"
    }
  ],
  "title": "Cyclic tri-adenylate controls a CARF-TM effector in type II Panoptes anti-phage systems",
  "title_text": "Cyclic tri-adenylate controls a CARF-TM effector in type II Panoptes anti-phage systems",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T13:21:18Z",
  "url": "https://research.draconitic.com/paper/dn4ap54whtyjm",
  "venue": "PLOS Biology",
  "versions": []
}