Cupric yersiniabactin is a virulence-associated superoxide dismutase mimic

Kaveri S. Chaturvedi, Chia S. Hung, Daryl E. Giblin, Saki Urushidani, Anthony M. Austin, Mary C. Dinauer, Jeffrey P. Henderson

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)551-561
Number of pages11
JournalACS Chemical Biology
Volume9
Issue number2
DOIs
StatePublished - Feb 21 2014

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