title: Cupric yersiniabactin is a virulence-associated superoxide dismutase mimic.
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.
authors.affiliation: 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.
authors.forename: Kaveri S
authors.initials: KS
authors.lastname: Chaturvedi
authors.forename: Chia S
authors.initials: CS
authors.lastname: Hung
authors.forename: Daryl E
authors.initials: DE
authors.lastname: Giblin
authors.forename: Saki
authors.initials: S
authors.lastname: Urushidani
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Austin
authors.forename: Mary C
authors.initials: MC
authors.lastname: Dinauer
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Henderson
mesh_terms: D000818:Animals; D002460:Cell Line; D002614:Chelating Agents / Q000737:chemistry / Q000378:metabolism; D003300:Copper / Q000737:chemistry / Q000378:metabolism*; D004926:Escherichia coli / Q000737:chemistry / Q000472:pathogenicity* / Q000502:physiology*; D004927:Escherichia coli Infections / Q000378:metabolism / Q000382:microbiology; D054884:Host-Pathogen Interactions; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D010636:Phenols / Q000737:chemistry / Q000378:metabolism*; D017262:Siderophores / Q000737:chemistry / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000737:chemistry / Q000378:metabolism; D013844:Thiazoles / Q000737:chemistry / Q000378:metabolism*
chemical_list: D002614:Chelating Agents; D010636:Phenols; D017262:Siderophores; D013844:Thiazoles; C104398:yersiniabactin; D003300:Copper; D013482:Superoxide Dismutase