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

Abstract

<p id="d4605020e237"> <i>Vibrio cholerae</i>, the causative agent of the diarrheal disease cholera, uses the syringe-like type VI secretion system (T6SS) to pierce adjacent cells. To investigate the role of the T6SS in invasion of intestines already occupied by symbiotic microbes, we genetically engineered <i>V. cholerae</i> strains and performed live 3D imaging in zebrafish to find that <i>V. cholerae</i> can expel a resident bacterial species in a T6SS-dependent manner. Surprisingly, the T6SS acts primarily to increase the strength of gut contractions, rather than directly killing the bacterial competitor. Deletion of an actin cross-linking domain from the T6SS returned gut activity to normal and eliminated <i>V. cholerae</i>’ <i>s</i> competitive advantage. These findings reveal a strategy by which pathogens can manipulate host biomechanics to redefine gut communities. </p><p class="first" id="d4605020e255">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. </p>