Bacterial cell division protein FtsZ complexes with a phage protein to activate bacterial immunity

Many antiphage defence systems directly bind a specific phage-encoded protein that acts similar to a pathogen-associated molecular pattern to activate an immune response. Such activation is often assumed to occur independent of host factors. Here we demonstrate that the antiphage defence protein CapRel^Ebc, a fused toxin–antitoxin system from Enterobacter chengduensis, senses the T7 phage-encoded protein Gp0.4 in complex with the host bacterial factor FtsZ, an essential cell division protein. During T7 infection, Gp0.4 sequesters monomeric FtsZ to block its polymerization and thereby inhibit bacterial cell division. Only the complex of Gp0.4–FtsZ, but neither protein alone, triggers CapRel^Ebc activity. Structural modelling and hydrogen–deuterium exchange mass spectrometry indicate that Gp0.4, FtsZ and CapRel^Ebc form a ternary complex that activates phage defence. Our work suggests that activation of bacterial immune systems does not always depend exclusively on phage-encoded triggers. Instead, activation can involve host factors targeted by phages, analogous to how eukaryotic innate immune systems detect pathogen-induced perturbations of host cells through effector-triggered immunity.