title: Quantitative metabolomics reveals an epigenetic blueprint for iron acquisition in uropathogenic Escherichia coli.
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.
authors.affiliation: Center for Women's Infectious Diseases Research, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Henderson
authors.forename: Jan R
authors.initials: JR
authors.lastname: Crowley
authors.forename: Jerome S
authors.initials: JS
authors.lastname: Pinkner
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Walker
authors.forename: Pablo
authors.initials: P
authors.lastname: Tsukayama
authors.forename: Walter E
authors.initials: WE
authors.lastname: Stamm
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Hooton
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Hultgren
mesh_terms: D002853:Chromatography, Liquid; D044127:Epigenesis, Genetic; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D004927:Escherichia coli Infections / Q000378:metabolism* / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D013058:Mass Spectrometry; D055432:Metabolomics / Q000379:methods*; D009154:Mutation; D012007:Rectum / Q000382:microbiology; D017262:Siderophores / Q000235:genetics* / Q000378:metabolism; D018709:Statistics, Nonparametric; D014552:Urinary Tract Infections / Q000378:metabolism* / Q000382:microbiology
chemical_list: D029968:Escherichia coli Proteins; D017262:Siderophores