The gut commensal bacteroides thetaiotaomicron exacerbates enteric infection through modification of the metabolic landscape

Meredith M. Curtis, Zeping Hu, Claire Klimko, Sanjeev Narayanan, Ralph Deberardinis, Vanessa Sperandio

Research output: Contribution to journalArticle

95 Scopus citations

Abstract

The enteric pathogen enterohemorrhagic Escherichia coli (EHEC) causes severe diarrhea, but the influence of the gut microbiota on EHEC infection is largely unknown. A predominant member of the microbiota, Bacteroides thetaiotaomicron (Bt), is resident at EHEC attachment sites. We show that Bt enhances EHEC virulence gene expression through the transcription factor Cra, which is functionally sensitive to sugar concentrations. This enhanced virulence accompanies increased formation of attaching and effacing (AE) lesions requisite for EHEC colonization. Infection with Citrobacter rodentium, a natural mouse pathogen homologous to EHEC, in Bt-reconstituted mice results in increased gut permeability along with exacerbated host pathology and mortality compared to mice deplete of microflora. Bt modifies the metabolite environment at infection sites, increasing metabolites involved in gluconeogenesis, with stark increases in succinate, which can be sensed by Cra. Our findings suggest that microbiota composition affects disease outcome and may explain links between microbiota composition and disease susceptibility.

Original languageEnglish (US)
Pages (from-to)759-769
Number of pages11
JournalCell Host and Microbe
Volume16
Issue number6
DOIs
Publication statusPublished - Dec 10 2014

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ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

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