title: Strain competition restricts colonization of an enteric pathogen and prevents colitis.
abstract: The microbiota is a major source of protection against intestinal pathogens; however, the specific bacteria and underlying mechanisms involved are not well understood. As a model of this interaction, we sought to determine whether colonization of the murine host with symbiotic non-toxigenic Bacteroides fragilis could limit acquisition of pathogenic enterotoxigenic B. fragilis We observed strain-specific competition with toxigenic B. fragilis, dependent upon type VI secretion, identifying an effector-immunity pair that confers pathogen exclusion. Resistance against host acquisition of a second non-toxigenic strain was also uncovered, revealing a broader function of type VI secretion systems in determining microbiota composition. The competitive exclusion of enterotoxigenic B. fragilis by a non-toxigenic strain limited toxin exposure and protected the host against intestinal inflammatory disease. Our studies demonstrate a novel role of type VI secretion systems in colonization resistance against a pathogen. This understanding of bacterial competition may be utilized to define a molecularly targeted probiotic strategy.
authors.affiliation: Department of Microbiology, University of Chicago, Chicago, IL, USA Interdisciplinary Scientist Training Program, University of Chicago, Chicago, IL, USA.
authors.forename: Aaron L
authors.initials: AL
authors.lastname: Hecht
authors.affiliation: Department of Microbiology, University of Chicago, Chicago, IL, USA Interdisciplinary Scientist Training Program, University of Chicago, Chicago, IL, USA.
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Casterline
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL, USA.
authors.forename: Zachary M
authors.identifier: 0000-0001-9748-7262
authors.initials: ZM
authors.lastname: Earley
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD, USA.
authors.forename: Young Ah
authors.initials: YA
authors.lastname: Goo
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Goodlett
authors.affiliation: Department of Microbiology, University of Chicago, Chicago, IL, USA Department of Pediatrics, University of Chicago, Chicago, IL, USA jbubeckw@peds.bsd.uchicago.edu.
authors.forename: Juliane
authors.identifier: 0000-0002-2755-3348
authors.initials: J
authors.lastname: Bubeck Wardenburg
mesh_terms: D000818:Animals; D000898:Antibiosis; D001441:Bacteroides fragilis / Q000145:classification / Q000235:genetics; D003092:Colitis / Q000139:chemically induced / Q000382:microbiology* / Q000473:pathology / Q000517:prevention & control; D004195:Disease Models, Animal; D054884:Host-Pathogen Interactions; D007109:Immunity; D007413:Intestinal Mucosa / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D056265:Microbial Interactions
keywords: colonization resistance; enterotoxigenic Bacteroides fragilis; in vivo strain competition; probiotics; type VI secretion