The siderophore yersiniabactin binds copper to protect pathogens during infection

Nat Chem Biol. 2012 Aug;8(8):731-6. doi: 10.1038/nchembio.1020. Epub 2012 Jul 8.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Catalytic Domain
  • Chromatography, Liquid
  • Copper / toxicity*
  • Escherichia coli Infections / microbiology
  • Female
  • Gene Expression Regulation, Bacterial / physiology
  • Humans
  • Mice
  • Mice, Inbred C3H
  • Phenols / chemistry
  • Phenols / metabolism*
  • Protein Binding
  • Tandem Mass Spectrometry
  • Thiazoles / chemistry
  • Thiazoles / metabolism*
  • Uropathogenic Escherichia coli / drug effects*
  • Uropathogenic Escherichia coli / metabolism*


  • Phenols
  • Thiazoles
  • yersiniabactin
  • Copper