Commensal pathogen competition impacts host viability.

While the structure and regulatory networks that govern type-six secretion system (T6SS) activity of are becoming increasingly clear, we know less about the role of T6SS in disease. Under laboratory conditions, uses T6SS to outcompete many Gram-negative species, including other strains and human commensal bacteria. However, the role of these interactions has not been resolved in an in vivo setting. We used the model of cholera to define the contribution of T6SS to pathogenesis. Here, we demonstrate that interactions between T6SS and host commensals impact pathogenesis. Inactivation of T6SS, or removal of commensal bacteria, attenuates disease severity. Reintroduction of the commensal, , into a germ-free host is sufficient to restore T6SS-dependent pathogenesis in which T6SS and host immune responses regulate viability. Together, our data demonstrate that T6SS acts on commensal bacteria to promote the pathogenesis of .