Kiwa is a bacterial membrane-embedded defence supercomplex activated by phage-induced membrane changes

Summary Bacteria and archaea deploy diverse, sophisticated defence systems to counter virus infection, yet many immunity mechanisms remain poorly understood. Here, we characterise the Kiwa defence system as a membrane-associated supercomplex that senses changes in the membrane induced by phage infection and plasmid conjugation. This supercomplex, comprising KwaA tetramers bound to KwaB dimers, as its basic repeating unit, detects structural stress via KwaA, activating KwaB, which binds ejected phage DNA through its DUF4868 domain, stalling phage DNA replication forks and thus disrupting replication and late transcription. We show that phage-encoded DNA mimic protein Gam, which inhibits RecBCD, also targets Kiwa through KwaB recognition. However, Gam binding to one defence system precludes its inhibition of the other. These findings reveal a distinct mechanism of bacterial immune coordination, where sensing of membrane disruptions and inhibitor partitioning enhance protection against phages and plasmids.