Copper import in Escherichia coli by the yersiniabactin metallophore system

Under high-copper conditions, yersiniabactin (Ybt) binds copper (Cu) to prevent toxicity. Ybt is now shown to mediate Cu import under low-Cu conditions through formation of a Cu(II)-Ybt complex resulting in metalation of a Cu-requiring enzyme. 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.