title: Metal selectivity by the virulence-associated yersiniabactin metallophore system.
abstract: Uropathogenic Escherichia coli secrete siderophores during human infections. Although siderophores are classically defined by their ability to bind iron(III) ions, the virulence-associated siderophore yersiniabactin was recently found to bind divalent copper ions during urinary tract infections. Here we use a mass spectrometric approach to determine the extent of non-iron(III) metal interactions by yersiniabactin and its TonB-dependent outer membrane importer FyuA. In addition to copper, iron and gallium ions, yersiniabactin was also observed to form stable nickel, cobalt, and chromium ion complexes. In E. coli, copper(II) and all other non-iron(III) yersiniabactin complexes were imported by FyuA in a TonB-dependent manner. Among metal-yersiniabactin complexes, copper(II) yersiniabactin is predicted to be structurally distinctive and was the only complex not to competitively inhibit iron(III) yersiniabactin import. These results are consistent with yersiniabactin as part of a metallophore system able to prioritize iron(III) complex uptake in high copper environments.
authors.affiliation: Center for Women's Infectious Diseases Research, Washington University School of Medicine, Box 8051, 660 S. Euclid Ave., St. Louis, Missouri 63110, USA. jhenderson@DOM.wustl.edu.
authors.forename: Eun-Ik
authors.initials: EI
authors.lastname: Koh
authors.forename: Chia S
authors.initials: CS
authors.lastname: Hung
authors.forename: Kaveri S
authors.initials: KS
authors.lastname: Parker
authors.forename: Jan R
authors.initials: JR
authors.lastname: Crowley
authors.forename: Daryl E
authors.initials: DE
authors.lastname: Giblin
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Henderson
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D002853:Chromatography, Liquid; D008670:Metals / Q000494:pharmacology*; D008954:Models, Biological; D008958:Models, Molecular; D010636:Phenols / Q000494:pharmacology*; D011789:Quantum Theory; D053719:Tandem Mass Spectrometry; D013844:Thiazoles / Q000494:pharmacology*; D056689:Uropathogenic Escherichia coli / Q000187:drug effects; D014774:Virulence / Q000187:drug effects
chemical_list: D001426:Bacterial Proteins; D008670:Metals; D010636:Phenols; D013844:Thiazoles; C104398:yersiniabactin
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