TY - JOUR
T1 - The siderophore yersiniabactin binds copper to protect pathogens during infection
AU - Chaturvedi, Kaveri S.
AU - Hung, Chia S.
AU - Crowley, Jan R.
AU - Stapleton, Ann E.
AU - Henderson, Jeffrey P.
N1 - Funding Information:
We would like to thank M. Gross, H. Rohrs and Y. Zhang for highresolution MS analysis and J. Pinker for assistance with smallmolecule purification. We are grateful to S. Hultgren, G. Marshall and B. Ford for helpful discussions. J.P.H. holds a Career Award for Medical Scientists from the BurroughsWellcome Fund. We additionally acknowledge US National Institutes of Health grants K12 HD00145909, AI 0717224, P30 HL10126301, P50 DK64540, U01 DK082315 and UL1 RR024992. MS was supported by P41RR00954, 8P41 GM10342235 (NCRR), P60DK20579 and P30DK56341.
PY - 2012/8
Y1 - 2012/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84864236433&partnerID=8YFLogxK
U2 - 10.1038/nchembio.1020
DO - 10.1038/nchembio.1020
M3 - Article
C2 - 22772152
AN - SCOPUS:84864236433
SN - 1552-4450
VL - 8
SP - 731
EP - 736
JO - Nature Chemical Biology
JF - Nature Chemical Biology
IS - 8
ER -