Metal selectivity by the virulence-associated yersiniabactin metallophore systemElectronic supplementary information (ESI) available. See DOI: 10.1039/c4mt00341a

Uropathogenic Escherichia coli secrete siderophores during human infections. Although siderophores are classically defined by their ability to bind iron( iii ) ions, the virulence-associated siderophore yersiniabactin was recently found to bind divalent copper ions during urinary tract infections. Here we use a mass spectrometric approach to determine the extent of non-iron( iii ) metal interactions by yersiniabactin and its TonB-dependent outer membrane importer FyuA. In addition to copper, iron and gallium ions, yersiniabactin was also observed to form stable nickel, cobalt, and chromium ion complexes. In E. coli , copper( ii ) and all other non-iron( iii ) yersiniabactin complexes were imported by FyuA in a TonB-dependent manner. Among metal-yersiniabactin complexes, copper( ii ) yersiniabactin is predicted to be structurally distinctive and was the only complex not to competitively inhibit iron( iii ) yersiniabactin import. These results are consistent with yersiniabactin as part of a metallophore system able to prioritize iron( iii ) complex uptake in high copper environments. Metal-yersiniabactin complexes are transported intact through the outer membrane receptor, FyuA, in a TonB-dependent manner in uropathogenic Escherichia coli .