RT Journal Article SR Electronic T1 Bacteriophages antagonize cGAS-like immunity in bacteria JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.03.30.486325 DO 10.1101/2022.03.30.486325 A1 Huiting, Erin A1 Athukoralage, Januka A1 Guan, Jingwen A1 Silas, Sukrit A1 Carion, Héloïse A1 Bondy-Denomy, Joseph YR 2022 UL http://biorxiv.org/content/early/2022/03/30/2022.03.30.486325.abstract AB The recently discovered cyclic-oligonucleotide-based anti-phage signaling system (CBASS) is related to eukaryotic cGAS-STING anti-viral immunity and is present in diverse prokaryotes. However, our understanding of how CBASS detects, inhibits, and co-evolves with phages is limited because CBASS function has only been studied in reconstituted heterologous systems. Here, we identify a phage-encoded CBASS antagonist (acbIIA1, anti-cbass type II-A gene 1) necessary for phage replication in the presence of endogenous CBASS immunity in Pseudomonas aeruginosa. acbIIA1 homologs are encoded by numerous lytic and temperate phages infecting Gram-negative bacteria. Deletion of acbIIA1 renders multiple phages susceptible to CBASS, but phages can then escape immune function via mutations in the major capsid gene. These mutants suggest that CBASS is activated by, or targets, the late-expressed phage capsid. Together, we establish a native model system to study CBASS and identify a common phage-encoded CBASS antagonist, demonstrating that CBASS is a bona fide anti-phage immune system in nature. Graphical AbstractCompeting Interest StatementThe authors have declared no competing interest.