title: Very long O-antigen chains enhance fitness during Salmonella-induced colitis by increasing bile resistance.
abstract: Intestinal inflammation changes the luminal habitat for microbes through mechanisms that have not been fully resolved. We noticed that the FepE regulator of very long O-antigen chain assembly in the enteric pathogen Salmonella enterica serotype Typhimurium (S. Typhimurium) conferred a luminal fitness advantage in the mouse colitis model. However, a fepE mutant was not defective for survival in tissue, resistance to complement or resistance to polymyxin B. We performed metabolite profiling to identify changes in the luminal habitat that accompany S. Typhimurium-induced colitis. This analysis suggested that S. Typhimurium-induced colitis increased the luminal concentrations of total bile acids. A mutation in fepE significantly reduced the minimal inhibitory concentration (MIC) of S. Typhimurium for bile acids in vitro. Oral administration of the bile acid sequestrant cholestyramine resin lowered the concentrations of total bile acids in colon contents during S. Typhimurium infection and significantly reduced the luminal fitness advantage conferred by the fepE gene in the mouse colitis model. Collectively, these data suggested that very long O-antigen chains function in bile acid resistance of S. Typhimurium, a property conferring a fitness advantage during luminal growth in the inflamed intestine.
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, Davis, California, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Crawford
authors.forename: A Marijke
authors.initials: AM
authors.lastname: Keestra
authors.forename: Sebastian E
authors.initials: SE
authors.lastname: Winter
authors.forename: Mariana N
authors.initials: MN
authors.lastname: Xavier
authors.forename: Renée M
authors.initials: RM
authors.lastname: Tsolis
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tolstikov
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Bäumler
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D002792:Cholestyramine Resin / Q000008:administration & dosage; D003092:Colitis / Q000382:microbiology*; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D009154:Mutation; D019081:O Antigens / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011112:Polymyxin B; D012481:Salmonella Infections, Animal / Q000276:immunology / Q000382:microbiology*; D012486:Salmonella typhimurium / Q000201:enzymology / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*
chemical_list: D001647:Bile Acids and Salts; D019081:O Antigens; D002792:Cholestyramine Resin; D011112:Polymyxin B