Periplasmic superoxide dismutase protects Salmonella from products of phagocyte NADPH-oxidase and nitric oxide synthase

Mary Ann De Groote, Urs A. Ochsner, Michael U. Shiloh, Carl Nathan, Joe M. McCord, Mary C. Dinauer, Stephen J. Libby, Andrés Vazquez-Torres, Yisheng Xu, Ferric C. Fang

Research output: Contribution to journalArticle

293 Scopus citations

Abstract

Superoxide dismutase (SOD) catalyzes the conversion of superoxide radical to hydrogen peroxide. Periplasmic localization of bacterial Cu,Zn- SOD has suggested a role of this enzyme in defense against extracellular phagocyte-derived reactive oxygen species. Sequence analysis of regions flanking the Salmonella typhimurium sodC gene encoding Cu,Zn-SOD demonstrates significant homology to A phage proteins, reflecting possible bacteriophage- mediated horizontal gene transfer of this determinant among pathogenic bacteria. Salmonella, a deficient in Cu,Zn-SOD has reduced survival in macrophages and attenuated virulence in mice, which can be restored by abrogation of either the phagocyte respiratory burst or inducible nitric oxide synthase. Moreover, a sodC mutant is extremely susceptible to the combination of superoxide and nitric oxide. These observations suggest that SOD protects periplasmic or inner membrane targets by diverting superoxide and limiting peroxynitrite formation, and they demonstrate the ability of the respiratory burst and nitric oxide synthase to synergistically kill microbial pathogens in vivo.

Original languageEnglish (US)
Pages (from-to)13997-14001
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number25
DOIs
StatePublished - Dec 9 1997

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