Bacteria use a diverse array of defence mechanisms to protect themselves from phage. Rotem Sorek and colleagues now describe a novel anti-phage pathway, that is widespread in bacteria, and operates through the synthesis of cyclic GMP–AMP (cGAMP). The authors show that the bacterial cGAS protein produces cGAMP following phage infection, leading to activation of its associated phospholipase, which results in degradation of the bacterial cell membrane and subsequent cell death. As this event occurs before the phage has an opportunity to replicate to high density, this protects the remaining bacterial population from infection, a mechanism known as abortive infection. Bioinformatic analyses reveal that bacterial cGAS couples with various different effectors, including a pore-forming protein, which they also show mediates protection. As the cGAS system in animals provides anti-viral defence, the authors propose that it may have a bacterial origin.
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