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Cupric Yersiniabactin Is a Virulence-Associated Superoxide Dismutase Mimic

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journal contribution
posted on 2015-12-17, 00:42 authored by Kaveri S. Chaturvedi, Chia S. Hung, Daryl E. Giblin, Saki Urushidani, Anthony M. Austin, Mary C. Dinauer, Jeffrey P. Henderson
Many Gram-negative bacteria interact with extracellular metal ions by expressing one or more siderophore types. Among these, the virulence-associated siderophore yersiniabactin (Ybt) is an avid copper chelator, forming stable cupric (Cu­(II)-Ybt) complexes that are detectable in infected patients. Here we show that Ybt-expressing E. coli are protected from intracellular killing within copper-replete phagocytic cells. This survival advantage is highly dependent upon the phagocyte respiratory burst, during which superoxide is generated by the NADPH oxidase complex. Chemical fractionation links this phenotype to a previously unappreciated superoxide dismutase (SOD)-like activity of Cu­(II)-Ybt. Unlike previously described synthetic copper-salicylate (Cu­(II)-SA) SOD mimics, the salicylate-based natural product Cu­(II)-Ybt retains catalytic activity at physiologically plausible protein concentrations. These results reveal a new virulence-associated adaptation based upon spontaneous assembly of a non-protein catalyst.

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