Ni(II) Uptake by Yersiniabactin, a Metallophore Produced by Uropathogenic E. coli

Metal ions can play dual roles as nutrients and toxins in the interaction between bacteria and their environments. E. coli isolates associated with urinary tract infections (UTIs) deploy siderophores, small molecule chelators defined by their ability to competitively bind iron(III) and deliver it to the cell. Yersiniabactin (Ybt) is a virulence‐associated siderophore of uropathogenic E. coli (UPEC) and was recently appreciated to also bind copper during UTIs in humans, forming Cu(II)‐Ybt complexes. Copper binding by Ybt was found to protect E. coli from copper toxicity and also to mediate controlled copper import for nutritional purposes. We have termed this process nutritional passivation. Ni(II) is generally less abundant than copper but is also a nutrient for E. coli with the potential for toxicity. We show here that the Ybt system of UPEC engages in an analogous nutritional passivation activity with Ni(II). Ybt passivates Ni(II) ions, protecting against Ni(II) toxicity in vitro . We also observe that UPEC can use Ni(II)‐Ybt as a nutrient source for nickel. Using quantitative LC‐MS/MS and isotope labeling, we detect import of Ni(II)‐Ybt and dissociation of the nickel, providing a nickel source for cellular enzymes. The metal‐free Ybt is secreted back outside of the cell to bind other metal ions. These findings broaden the spectrum of Ybt activity, reinforcing its value to UPEC as a true metallophore, capable of binding and importing not only iron, but also copper and nickel. Support or Funding Information J.P.H. acknowledges National Institute of Diabetes and Digestive and Kidney Diseases grant R01DK099534. A.E.R. was supported by the Mr. and Mrs. Spencer T. Olin Fellowship for Women in Graduate Study. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .