title: The gut commensal Bacteroides thetaiotaomicron exacerbates enteric infection through modification of the metabolic landscape.
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.
authors.affiliation: Department of Microbiology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Meredith M
authors.initials: MM
authors.lastname: Curtis
authors.affiliation: Children's Medical Center Research Institute, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Zeping
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Children's Medical Center Research Institute, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Klimko
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS 66506, USA.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Narayanan
authors.affiliation: Children's Medical Center Research Institute, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Ralph
authors.initials: R
authors.lastname: Deberardinis
authors.affiliation: Department of Microbiology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: vanessa.sperandio@utsouthwestern.edu.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Sperandio
mesh_terms: D000818:Animals; D001439:Bacteroides / Q000235:genetics / Q000502:physiology*; D044082:Citrobacter rodentium / Q000235:genetics / Q000502:physiology; D004756:Enterobacteriaceae Infections / Q000378:metabolism* / Q000382:microbiology*; D054324:Enterohemorrhagic Escherichia coli / Q000235:genetics / Q000502:physiology; D005260:Female; D041981:Gastrointestinal Tract / Q000378:metabolism* / Q000382:microbiology*; D005943:Gluconeogenesis; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D064307:Microbiota; D019802:Succinic Acid / Q000378:metabolism; D013559:Symbiosis
chemical_list: D019802:Succinic Acid