Very Long O-antigen Chains Enhance Fitness during Salmonella-induced Colitis by Increasing Bile Resistance

PLoS Pathogens

A. Marijke Keestra¹  Sebastian E. Winter¹  Mariana N. Xavier¹  Robert W. Crawford¹  Andreas J. Bäumler¹  Renée M. Tsolis¹  Vladimir Tolstikov² 

[1] Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, Davis, California, United States of America;Metabolomics Core Laboratory, Genome Center, University of California at Davis, Davis, California, United States of America

关键词: Salmonella typhimurium;    Bile;    Colitis;    Metabolites;    Streptomycin;    Animal models of infection;    Colon;    Plasmid construction;   

DOI  :  10.1371/journal.ppat.1002918

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY