Regulated virulence controls the ability of a pathogen to compete with the gut microbiota

Science. 2012 Jun 8;336(6086):1325-9. doi: 10.1126/science.1222195. Epub 2012 May 10.

Abstract

The virulence mechanisms that allow pathogens to colonize the intestine remain unclear. Here, we show that germ-free animals are unable to eradicate Citrobacter rodentium, a model for human infections with attaching and effacing bacteria. Early in infection, virulence genes were expressed and required for pathogen growth in conventionally raised mice but not germ-free mice. Virulence gene expression was down-regulated during the late phase of infection, which led to relocation of the pathogen to the intestinal lumen where it was outcompeted by commensals. The ability of commensals to outcompete C. rodentium was determined, at least in part, by the capacity of the pathogen and commensals to grow on structurally similar carbohydrates. Thus, pathogen colonization is controlled by bacterial virulence and through competition with metabolically related commensals.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Load
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Bacteroides / growth & development*
  • Citrobacter rodentium / genetics
  • Citrobacter rodentium / growth & development
  • Citrobacter rodentium / immunology
  • Citrobacter rodentium / pathogenicity*
  • Enterobacteriaceae Infections / immunology
  • Enterobacteriaceae Infections / microbiology*
  • Escherichia coli / growth & development*
  • Feces / microbiology
  • Gene Expression Regulation, Bacterial
  • Germ-Free Life
  • Intestinal Mucosa / microbiology*
  • Intestines / microbiology*
  • Metagenome*
  • Mice
  • Mice, Inbred C57BL
  • Microbial Interactions*
  • Specific Pathogen-Free Organisms
  • Virulence Factors / genetics
  • Virulence Factors / metabolism

Substances

  • Bacterial Proteins
  • Virulence Factors