Bacterial 2',3'-cGAMP signaling induces membrane splitting in antiphage CBASS immunity

Bacterial cyclic-oligonucleotide-based antiphage signaling systems (CBASS) are evolutionarily related to the mammalian cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway. The bacterial CdnB-Cap14 CBASS system is notable for producing 2',3'-cyclic GMP-AMP (2',3'-cGAMP), the same second messenger used by the mammalian cGAS-STING pathway; however, its functional mechanism has remained unclear. Here, we show that CdnB-Cap14 protects against phage infection through abortive infection (Abi) by triggering cell death. Structures of apo CdnB^ΔC and its complexes with ATP and guanosine triphosphate (GTP), together with inactive and activated 2',3'-cGAMP-bound Cap14, reveal that CdnB is autoinhibited by its C-terminal AGS-C domain and becomes activated by DNA together with intracellular ATP/GTP depletion to synthesize 2',3'-cGAMP in vitro. This signal drives Cap14 assembly from dimers into zipper-like two-layered filaments that partition the membrane and disrupt its integrity. We further show that phage-encoded Acb2 sequesters 2',3'-cGAMP to block signaling. These findings reveal mechanistic parallels between bacterial CBASS and eukaryotic cGAS-STING immunity and provide a molecular basis for therapeutic engineering.