TheVibrio choleraetype VI secretion system can modulate host intestinal mechanics to displace gut bacterial symbionts

Abstract

Host-associated microbiota help defend against bacterial pathogens; however, the mechanisms by which pathogens overcome this defense remain largely unknown. We developed a zebrafish model and used live imaging to directly study how the human pathogenVibrio choleraeinvades the intestine. The gut microbiota of fish monocolonized by symbiotic strainAeromonas veroniiwas displaced byV. choleraeexpressing its type VI secretion system (T6SS), a syringe-like apparatus that deploys effector proteins into target cells. Surprisingly, displacement was independent of T6SS-mediated killing ofA. veronii, driven instead by T6SS-induced enhancement of zebrafish intestinal movements that led to expulsion of the resident microbiota by the host. Deleting an actin cross-linking domain from the T6SS apparatus returned intestinal motility to normal and thwarted expulsion, without weakeningV. cholerae’s ability to killA. veroniiin vitro. Our finding that bacteria can manipulate host physiology to influence intermicrobial competition has implications for both pathogenesis and microbiome engineering.