PERIPLASMIC SUPEROXIDE-DISMUTASE PROTECTS SALMONELLA FROM PRODUCTS OFPHAGOCYTE NADPH-OXIDASE AND NITRIC-OXIDE SYNTHASE

Superoxide dismutase (SOD) catalyzes the conversion of superoxide radi cal to hydrogen peroxide. Periplasmic localization of bacterial Cu,Zn- SOD has suggested a role of this enzyme in defense against extracellul ar phagocyte-derived reactive oxygen species. Sequence analysis of reg ions flanking the Salmonella typhimurium sodC gene encoding Cu,Zn-SOD demonstrates significant homology toh phage proteins, reflecting possi ble bacteriophage-mediated horizontal gene transfer of this determinan t among pathogenic bacteria. Salmonella deficient in Cu,Zn-SOD has red uced survival in macrophages and attenuated virulence in mice, which c an be restored by abrogation of either the phagocyte respiratory burst or inducible nitric oxide synthase. Moreover, a sodC mutant is extrem ely susceptible to the combination of superoxide and nitric oxide. The se observations suggest that SOD protects periplasmic or inner membran e 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.