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Publication Abstract from PubMed

A fundamental strategy of eukaryotic antiviral immunity involves the cGAS enzyme, which synthesizes 2',3'-cGAMP and activates the effector STING. Diverse bacteria contain cGAS-like enzymes that produce cyclic oligonucleotides and induce anti-phage activity, known as CBASS. However, this activity has only been demonstrated through heterologous expression. Whether bacteria harboring CBASS antagonize and co-evolve with phages is unknown. Here, we identified an endogenous cGAS-like enzyme in Pseudomonas aeruginosa that generates 3',3'-cGAMP during phage infection, signals to a phospholipase effector, and limits phage replication. In response, phages express an anti-CBASS protein ("Acb2") that forms a hexamer with three 3',3'-cGAMP molecules and reduces phospholipase activity. Acb2 also binds to molecules produced by other bacterial cGAS-like enzymes (3',3'-cUU/UA/UG/AA) and mammalian cGAS (2',3'-cGAMP), suggesting broad inhibition of cGAS-based immunity. Upon Acb2 deletion, CBASS blocks lytic phage replication and lysogenic induction, but rare phages evade CBASS through major capsid gene mutations. Altogether, we demonstrate endogenous CBASS anti-phage function and strategies of CBASS inhibition and evasion.

Bacteriophages inhibit and evade cGAS-like immune function in bacteria.,Huiting E, Cao X, Ren J, Athukoralage JS, Luo Z, Silas S, An N, Carion H, Zhou Y, Fraser JS, Feng Y, Bondy-Denomy J Cell. 2023 Jan 31:S0092-8674(22)01584-7. doi: 10.1016/j.cell.2022.12.041. PMID:36750095^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.