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

PLoS Pathogens

Jeffrey P. Henderson¹  Jennifer N. Walker¹  Scott J. Hultgren²  Thomas M. Hooton³  Walter E. Stamm³  Pablo Tsukayama³  Jan R. Crowley⁴  Jerome S. Pinkner⁴ 

[1] Center for Women's Infectious Diseases Research, Washington University School of Medicine, St. Louis, Missouri, United States of America;Department of Internal Medicine, University of Washington, Seattle, Washington, United States of America;Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America;Division of Infectious Diseases, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America

关键词: Rectum;    Urinary tract infections;    Metabolomics;    Biosynthesis;    Bacterial pathogens;    Genotyping;    Stable isotopes;    Liquid chromatography-mass spectrometry;   

DOI  :  10.1371/journal.ppat.1000305

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY