Periplasmic superoxide dismutase protects Salmonella from products of phagocyte NADPH-oxidase and nitric oxide synthase.
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 lambda phage proteins, reflecting possible bacteriophage-mediated horizontal gene transfer of this determinant among pathogenic bacteria. Salmonella 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.
De Groote
M A
MA
Department of Medicine, University of Colorado Health Sciences Center, 4200 E. Ninth Avenue, Denver, CO 80262, USA.
Ochsner
U A
UA
Shiloh
M U
MU
Nathan
C
C
McCord
J M
JM
Dinauer
M C
MC
Libby
S J
SJ
Vazquez-Torres
A
A
Xu
Y
Y
Fang
F C
FC
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D066298:In Vitro Techniques; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009154:Mutation; D019255:NADPH Oxidases / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D010586:Phagocytes / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst; D012481:Salmonella Infections, Animal / Q000378:metabolism; D012486:Salmonella typhimurium / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
D017931:DNA Primers; D017382:Reactive Oxygen Species; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D019255:NADPH Oxidases