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

Robert W. Crawford, A. Marijke Keestra, Sebastian E. Winter, Mariana N. Xavier, Renee M Tsolis, Vladimir Tolstikov, Andreas J Baumler

Research output: Contribution to journalArticle

30 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere1002918
JournalPLoS Pathogens
Volume8
Issue number9
DOIs
StatePublished - Sep 2012

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O Antigens
Colitis
Bile
Salmonella
Bile Acids and Salts
Ecosystem
Cholestyramine Resin
Tissue Survival
Polymyxin B
Salmonella enterica
Intestines
Oral Administration
Serogroup
Colon
Inflammation
Mutation
Growth
Infection
Genes

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Very Long O-antigen Chains Enhance Fitness during Salmonella-induced Colitis by Increasing Bile Resistance. / Crawford, Robert W.; Keestra, A. Marijke; Winter, Sebastian E.; Xavier, Mariana N.; Tsolis, Renee M; Tolstikov, Vladimir; Baumler, Andreas J.

In: PLoS Pathogens, Vol. 8, No. 9, e1002918, 09.2012.

Research output: Contribution to journalArticle

Crawford, Robert W. ; Keestra, A. Marijke ; Winter, Sebastian E. ; Xavier, Mariana N. ; Tsolis, Renee M ; Tolstikov, Vladimir ; Baumler, Andreas J. / Very Long O-antigen Chains Enhance Fitness during Salmonella-induced Colitis by Increasing Bile Resistance. In: PLoS Pathogens. 2012 ; Vol. 8, No. 9.
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