title: Bile Salts Modulate the Mucin-Activated Type VI Secretion System of Pandemic Vibrio cholerae.
abstract: The causative agent of cholera, Vibrio cholerae, regulates its diverse virulence factors to thrive in the human small intestine and environmental reservoirs. Among this pathogen's arsenal of virulence factors is the tightly regulated type VI secretion system (T6SS). This system acts as an inverted bacteriophage to inject toxins into competing bacteria and eukaryotic phagocytes. V. cholerae strains responsible for the current 7th pandemic activate their T6SS within the host. We established that T6SS-mediated competition occurs upon T6SS activation in the infant mouse, and that this system is functional under anaerobic conditions. When investigating the intestinal host factors mucins (a glycoprotein component of mucus) and bile for potential regulatory roles in controlling the T6SS, we discovered that once mucins activate the T6SS, bile acids can further modulate T6SS activity. Microbiota modify bile acids to inhibit T6SS-mediated killing of commensal bacteria. This interplay is a novel interaction between commensal bacteria, host factors, and the V. cholerae T6SS, showing an active host role in infection.
authors: Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
authors: Verena
authors: V
authors: Bachmann
authors: Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
authors: Benjamin
authors: B
authors: Kostiuk
authors: Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
authors: Daniel
authors: D
authors: Unterweger
authors: Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
authors: Laura
authors: L
authors: Diaz-Satizabal
authors: Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
authors: Stephen
authors: S
authors: Ogg
authors: Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
authors: Stefan
authors: S
authors: Pukatzki
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism*; D002771:Cholera / Q000453:epidemiology / Q000378:metabolism* / Q000382:microbiology; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D054884:Host-Pathogen Interactions; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology; D008297:Male; D051379:Mice; D009077:Mucins / Q000378:metabolism*; D058873:Pandemics; D000069376:Type VI Secretion Systems / Q000235:genetics / Q000378:metabolism*; D014734:Vibrio cholerae / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D001647:Bile Acids and Salts; D009077:Mucins; D000069376:Type VI Secretion Systems