Document Detail

Very long O-antigen chains enhance fitness during Salmonella-induced colitis by increasing bile resistance.
MedLine Citation:
PMID:  23028318     Owner:  NLM     Status:  MEDLINE    
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.
Robert W Crawford; A Marijke Keestra; Sebastian E Winter; Mariana N Xavier; Renée M Tsolis; Vladimir Tolstikov; Andreas J Bäumler
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-09-20
Journal Detail:
Title:  PLoS pathogens     Volume:  8     ISSN:  1553-7374     ISO Abbreviation:  PLoS Pathog.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-10-02     Completed Date:  2013-05-09     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  101238921     Medline TA:  PLoS Pathog     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e1002918     Citation Subset:  IM    
Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, Davis, California, USA.
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MeSH Terms
Bile Acids and Salts / metabolism*
Cholestyramine Resin / administration & dosage
Colitis / microbiology*
Disease Models, Animal
Mice, Inbred C57BL
Microbial Sensitivity Tests
O Antigens / chemistry,  genetics*,  metabolism
Polymyxin B
Salmonella Infections, Animal / immunology,  microbiology*
Salmonella typhimurium / enzymology,  genetics,  growth & development,  pathogenicity*
Grant Support
Reg. No./Substance:
0/Bile Acids and Salts; 0/O Antigens; 11041-12-6/Cholestyramine Resin; 1404-26-8/Polymyxin B

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