Defending against the Type Six Secretion System: beyond Immunity Genes

The bacterial type six secretion system (T6SS) delivers toxic effector proteins into neighboring cells, but bacteria must protect themselves against their own T6SS. Immunity genes are the best-characterized defenses, protecting against specific cognate effectors. However, the prevalence of the T6SS and the coexistence of species with heterologous T6SSs suggest evolutionary pressure selecting for additional defenses against it. Here we review defenses against the T6SS beyond self-associated immunity genes, such as diverse stress responses that can recognize T6SS-inflicted damage and coordinate induction of molecular armor, repair pathways, and overall survival. Some of these stress responses are required for full survival even in the presence of immunity genes. Finally, we propose that immunity gene-independent protection is, mechanistically, bacterial innate immunity and that such defenses and the T6SS have co-evolved and continue to shape one another in polymicrobial communities.