Quantitative Metabolomics Reveals an Epigenetic Blueprint for Iron Acquisition in Uropathogenic Escherichia Coli

PLoS Pathog. 2009 Feb;5(2):e1000305. doi: 10.1371/journal.ppat.1000305. Epub 2009 Feb 20.

Abstract

Bacterial pathogens are frequently distinguished by the presence of acquired genes associated with iron acquisition. The presence of specific siderophore receptor genes, however, does not reliably predict activity of the complex protein assemblies involved in synthesis and transport of these secondary metabolites. Here, we have developed a novel quantitative metabolomic approach based on stable isotope dilution to compare the complement of siderophores produced by Escherichia coli strains associated with intestinal colonization or urinary tract disease. Because uropathogenic E. coli are believed to reside in the gut microbiome prior to infection, we compared siderophore production between urinary and rectal isolates within individual patients with recurrent UTI. While all strains produced enterobactin, strong preferential expression of the siderophores yersiniabactin and salmochelin was observed among urinary strains. Conventional PCR genotyping of siderophore receptors was often insensitive to these differences. A linearized enterobactin siderophore was also identified as a product of strains with an active salmochelin gene cluster. These findings argue that qualitative and quantitative epi-genetic optimization occurs in the E. coli secondary metabolome among human uropathogens. Because the virulence-associated biosynthetic pathways are distinct from those associated with rectal colonization, these results suggest strategies for virulence-targeted therapies.

Publication types

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

MeSH terms

  • Chromatography, Liquid
  • Epigenesis, Genetic
  • Escherichia coli / genetics*
  • Escherichia coli / metabolism
  • Escherichia coli Infections / metabolism*
  • Escherichia coli Infections / microbiology
  • Escherichia coli Proteins / genetics*
  • Escherichia coli Proteins / metabolism
  • Female
  • Gene Expression
  • Humans
  • Mass Spectrometry
  • Metabolomics / methods*
  • Mutation
  • Rectum / microbiology
  • Siderophores / genetics*
  • Siderophores / metabolism
  • Statistics, Nonparametric
  • Urinary Tract Infections / metabolism*
  • Urinary Tract Infections / microbiology

Substances

  • Escherichia coli Proteins
  • Siderophores