Periplasmic Binding Protein YiuA Enables Yersinia pestis to Scavenge Fe(III)-Catechol Siderophores

Yersinia pestis, the pathogen causing plague, requires iron to grow. Y. pestis employs several uptake pathways for iron, including the siderophore yersiniabactin, as well as hemin and inorganic iron. The Y. pestis iron assimilation repertoire further harbors the uncharacterized YiuRABC pathway, presumed to transport an unidentified Fe(III)-siderophore(s). Through intrinsic fluorescence quenching of the periplasmic binding protein YiuA, we discovered that YiuA displays high affinity toward Fe(III) complexes of the hydrolysis products of enterobactin, Fe(III)-[di(DHB-^LSer)] and Fe(III)-[DHB-^LSer]₂, with K_d values of 27.6 ± 4.2 nM and 28.2 ± 6.9 nM, respectively, as well as the bis-catechol siderophore butanochelin, with K_d 0.76 ± 0.17 nM. By comparison, YiuA has a much weaker affinity for intact Fe(III)-enterobactin, K_d 444.7 ± 20.6 nM. Electronic circular dichroism spectroscopy reveals YiuA has a strong preference for binding Λ configured Fe(III)-siderophores, which can be achieved with the Fe(III) bis-catechol complexes but not Fe(III)-enterobactin.