Abstract |
Bacterial pathogens secrete chemically diverse iron chelators called siderophores, which may exert additional distinctive functions in vivo. Among these, uropathogenic Escherichia coli often coexpress the virulence-associated siderophore yersiniabactin (Ybt) with catecholate siderophores. Here we used a new MS screening approach to reveal that Ybt is also a physiologically favorable Cu(II) ligand. Direct MS detection of the resulting Cu(II)-Ybt complex in mice and humans with E. coli urinary tract infections demonstrates copper binding to be a physiologically relevant in vivo interaction during infection. Ybt expression corresponded to higher copper resistance among human urinary tract isolates, suggesting a protective role for this interaction. Chemical and genetic characterization showed that Ybt helps bacteria resist copper toxicity by sequestering host-derived Cu(II) and preventing its catechol-mediated reduction to Cu(I). Together, these studies reveal a new virulence-associated function for Ybt that is distinct from iron binding.
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Authors | Kaveri S Chaturvedi, Chia S Hung, Jan R Crowley, Ann E Stapleton, Jeffrey P Henderson |
Journal | Nature chemical biology
(Nat Chem Biol)
Vol. 8
Issue 8
Pg. 731-6
(Aug 2012)
ISSN: 1552-4469 [Electronic] United States |
PMID | 22772152
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Phenols
- Thiazoles
- yersiniabactin
- Copper
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Topics |
- Animals
- Catalytic Domain
- Chromatography, Liquid
- Copper
(toxicity)
- Escherichia coli Infections
(microbiology)
- Female
- Gene Expression Regulation, Bacterial
(physiology)
- Humans
- Mice
- Mice, Inbred C3H
- Phenols
(chemistry, metabolism)
- Protein Binding
- Tandem Mass Spectrometry
- Thiazoles
(chemistry, metabolism)
- Uropathogenic Escherichia coli
(drug effects, metabolism)
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