PT  - JOURNAL ARTICLE
AU  - Huiting, Erin
AU  - Athukoralage, Januka
AU  - Guan, Jingwen
AU  - Silas, Sukrit
AU  - Carion, Héloïse
AU  - Bondy-Denomy, Joseph
TI  - Bacteriophages antagonize cGAS-like immunity in bacteria
AID  - 10.1101/2022.03.30.486325
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.03.30.486325
4099  - http://biorxiv.org/content/early/2022/03/30/2022.03.30.486325.short
4100  - http://biorxiv.org/content/early/2022/03/30/2022.03.30.486325.full
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.