title: The siderophore yersiniabactin binds copper to protect pathogens during infection.
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.
authors: Center for Women's Infectious Diseases Research, Washington University School of Medicine, St. Louis, MO, USA.
authors: Kaveri S
authors: KS
authors: Chaturvedi
authors: Chia S
authors: CS
authors: Hung
authors: Jan R
authors: JR
authors: Crowley
authors: Ann E
authors: AE
authors: Stapleton
authors: Jeffrey P
authors: JP
authors: Henderson
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D002853:Chromatography, Liquid; D003300:Copper / Q000633:toxicity*; D004927:Escherichia coli Infections / Q000382:microbiology; D005260:Female; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D010636:Phenols / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D053719:Tandem Mass Spectrometry; D013844:Thiazoles / Q000737:chemistry / Q000378:metabolism*; D056689:Uropathogenic Escherichia coli / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D010636:Phenols; D013844:Thiazoles; C104398:yersiniabactin; D003300:Copper