{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:48:50Z","timestamp":1789624130597,"version":"build-2803163510"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/Z517240\/1"],"award-info":[{"award-number":["BB\/Z517240\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["101018608"],"award-info":[{"award-number":["101018608"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosbiology.org"],"crossmark-restriction":false},"short-container-title":["PLoS Biol"],"abstract":"<jats:p>\n                    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\n                    <jats:bold>-<\/jats:bold>\n                    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 2TM\u03b2 to halt the phage infection cycle. Here, we investigate the type II Panoptes system, demonstrating that it generates cyclic tri-adenylate (cA\n                    <jats:sub>3<\/jats:sub>\n                    ) to maintain a CRISPR-associated Rossmann fold-transmembrane (CARF-TM) effector in an inactive, dimeric state. When cA\n                    <jats:sub>3<\/jats:sub>\n                    is sequestered or degraded, the CARF protein undergoes conformational changes. In vivo, the absence of cA\n                    <jats:sub>3<\/jats:sub>\n                    results in membrane disruption and growth arrest. Type II Panoptes provides defence against phages that express the cA\n                    <jats:sub>3<\/jats:sub>\n                    -degrading enzyme Acb1; phage escapers introduce mutations into the\n                    <jats:italic>acb1<\/jats:italic>\n                    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                  <\/jats:p>","DOI":"10.1371\/journal.pbio.3003934","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T17:22:11Z","timestamp":1789492931000},"page":"e3003934","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cyclic tri-adenylate controls a CARF-TM effector in type II Panoptes anti-phage systems"],"prefix":"10.1371","volume":"24","author":[{"given":"Sabine","family":"Gr\u00fcschow","sequence":"first","affiliation":[{"name":"University of St Andrews","place":["St Andrews, United Kingdom"],"department":["School of Biology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Wotherspoon","sequence":"additional","affiliation":[{"name":"University of St Andrews","place":["St Andrews, United 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