Kiwa rescues RecBCD for anti-phage activity

Abstract

Bacteria have evolved numerous defence systems to combat phage infection, but our understanding of the underlying mechanisms is limited beyond their antiviral function. Here, we provide mechanistic insights into the Kiwa defence system, which is composed of two proteins, the transmembrane protein KwaA and the DUF4868 domain-containing protein KwaB. Using Kiwa from Escherichia coli ECOR8 and ECOR12, we found that KwaA detects phage infection by sensing inhibition of the host RNA polymerase. Consequently, the inhibitory effect of KwaA on the effector protein KwaB is relieved, which results in decreased phage DNA replication efficiency through a RecBCD-dependent pathway. Notably, Kiwa restores RecBCD activity even against phages that encode anti-RecBCD proteins. Our findings also reveal that KwaB has antiphage activity in the absence of both KwaA and phage trigger, but the conserved two-protein Kiwa operon implies that strict regulation of KwaB activity by KwaA is necessary to prevent potential auto-immunity.