1.B.162. The Cyclic oligonucleotide-based Antiphage Signaling System (CBASS) Family
Cyclic oligonucleotide-based antiphage signaling systems (CBASS) are encoded by antiviral defense operons that protect bacteria from phage replication. Duncan-Lowey et al. 2021 iendtified a widespread class of CBASS transmembrane (TM) effector proteins that respond to antiviral nucleotide signals and limit phage propagation through direct membrane disruption. Crystal structures of the Yersinia TM effector, Cap15, revealed a compact 8-stranded beta-barrel scaffold that forms a cyclic dinucleotide receptor domain that oligomerizes upon activation. They demonstrated that activated Cap15 relocalizes throughout the cell and specifically induces rupture of the inner membrane. Screening for active effectors, they identified the functions of distinct families of CBASS TM effectors and demonstrated that cell death via disruption of inner-membrane integrity is a common mechanism of defense. These results reveal the function of the most prominent class of effector protein in CBASS immunity and define disruption of the inner membrane as a widespread strategy of abortive infection in bacterial phage defense (Duncan-Lowey et al. 2021).