Commensal-Pathogen Competition Impacts Host Viability

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