Commensal pathogen competition impacts host viability.

Abstract

While the structure and regulatory networks that govern type-six secretion system (T6SS) activity of <i>Vibrio cholerae</i> are becoming increasingly clear, we know less about the role of T6SS in disease. Under laboratory conditions, <i>V. cholerae</i> uses T6SS to outcompete many Gram-negative species, including other <i>V. cholerae</i> strains and human commensal bacteria. However, the role of these interactions has not been resolved in an in vivo setting. We used the <i>Drosophila melanogaster</i> model of cholera to define the contribution of T6SS to <i>V. cholerae</i> 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, <i>Acetobacter pasteurianus</i>, 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 <i>V. cholerae</i>.