Tail assembly interference is a common strategy in the repertoire of prokaryotic immune systems. Escherichia coli

Prokaryotic immune systems employ various strategies to interfere with the transfer and function of mobile genetic elements. Although numerous immune systems can recognize phage structural components to activate their functions, none have been identified with the capacity to target and inhibit a phage structural component's function. In this study, we present the discovery of a prevalent family of immune systems known as Tai (tail assembly inhibition). These systems specifically block tail assembly formation, leading to the release of tailless phages incapable of infecting new hosts. Notably, we observed that some Tai-positive phages also encode an associated counter-defense mechanism to prevent autoimmunity. This counter-defense mechanism is expressed exclusively during the phage lytic cycle to allow for tail formation. Interestingly, the immune and counter-defense genes are organized in a non-contiguous operon, enabling their coordinated expression. Our results unveil a novel strategy that safeguards bacteria from phage attacks.