The <i>Vibrio cholerae</i> type 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 pathogen <i>Vibrio cholerae</i> invades the intestine. The gut microbiota of fish monocolonized by symbiotic strain <i>Aeromonas veronii</i> was displaced by <i>V. cholerae</i> expressing 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 of <i>A. veronii</i>, 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 weakening <i>V. cholerae</i>'s ability to kill <i>A. veronii</i> in vitro. Our finding that bacteria can manipulate host physiology to influence intermicrobial competition has implications for both pathogenesis and microbiome engineering.