Type VI Secretion System Can Modulate Host Intestinal Mechanics to Displace Commensal Gut Bacteria*

Host-associated microbiota help defend against bacterial pathogens; the physical and chemical mechanisms by which pathogens overcome this defense, however, remain largely unknown. We applied live imaging to larval zebrafish to study how the human pathogen Vibrio cholerae invades the intestine. The gut microbiota of fish mono-colonized by commensal strain Aeromonas veronii was displaced by V. cholerae expressing its Type VI Secretion System (T6SS), a syringe-like apparatus that deploys toxins into target cells. Surprisingly, displacement was independent of T6SS-mediated killing of Aeromonas, driven instead by T6SS-induced enhancement of zebrafish intestinal movements that led to expulsion of the resident commensal by the host. Deleting an actin crosslinking domain from the T6SS apparatus returned intestinal motility to normal and thwarted expulsion, without weakening V. cholerae's ability to kill Aeromonas in vitro. Our finding that bacteria can manipulate host physiology to influence inter-microbial competition has implications for both pathogenesis and microbiome engineering.