Abstract
Copper plays a dual role as a nutrient and a toxin during bacterial infections. While uropathogenic Escherichia coli (UPEC) strains can use the copper-binding metallophore yersiniabactin (Ybt) to resist copper toxicity, Ybt also converts bioavailable copper to Cu(II)–Ybt in low-copper conditions. Although E. coli have long been considered to lack a copper import pathway, we observed Ybt-mediated copper import in UPEC using canonical Fe(III)–Ybt transport proteins. UPEC removed copper from Cu(II)–Ybt with subsequent re-export of metal-free Ybt to the extracellular space. Copper released through this process became available to an E. coli cuproenzyme (the amine oxidase TynA), linking this import pathway to a nutrient acquisition function. Ybt-expressing E. coli thus engage in nutritional passivation, a strategy of minimizing a metal ion's toxicity while preserving its nutritional availability. Copper acquisition through this process may contribute to the marked virulence defect of Ybt-transport-deficient UPEC.
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Acknowledgements
J.P.H. holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund and acknowledges National Institute of Diabetes and Digestive and Kidney Diseases grants R01DK099534 and P50DK064540. A.E.R. was supported by the Mr. and Mrs. Spencer T. Olin Fellowship for Women in Graduate Study. ICP-MS was supported by the Nano Research Facility at Washington University in St. Louis. The funders had no role in study design, data collection and interpretation, or in the decision to submit the work for publication. We thank Z. Zou, J. Walker, L. Robinson, K. Tamadonfar and S. Krieger for technical assistance, and S. Ohlemacher for helpful discussion.
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E.K., A.E.R. and J.P.H. conceived and designed the experiments. E.K. and A.E.R. performed the biochemical experiments and follow-up studies. A.E.R. conducted the ICP-MS analysis. E.K. and N.B. performed the 64Cu radiolabeling experiments. E.K., A.E.R., N.B., B.E.R. and J.P.H. analyzed the data. E.K., A.E.R. and J.P.H. wrote the paper.
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Koh, EI., Robinson, A., Bandara, N. et al. Copper import in Escherichia coli by the yersiniabactin metallophore system. Nat Chem Biol 13, 1016–1021 (2017). https://doi.org/10.1038/nchembio.2441
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DOI: https://doi.org/10.1038/nchembio.2441
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