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ACS Chem Biol. 2014 Feb 21;9(2):551-61. doi: 10.1021/cb400658k. Epub 2013 Dec 11.

Cupric yersiniabactin is a virulence-associated superoxide dismutase mimic.

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Center for Women's Infectious Diseases Research, ‡Division of Infectious Diseases, §Department of Internal Medicine, ∥Department of Chemistry, ⊥Department of Pediatrics, and #Department of Pathology and Immunology, Washington University School of Medicine , St. Louis, Missouri 63110, United States.


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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