Glucose 6-phosphate dehydrogenase is required for Salmonella typhimurium virulence and resistance to reactive oxygen and nitrogen intermediates.
Salmonella typhimurium zwf mutants lacking glucose 6-phosphate dehydrogenase (G6PD) activity have increased susceptibility to reactive oxygen and nitrogen intermediates as well as attenuated virulence in mice. Abrogation of the phagocyte respiratory burst oxidase during experimental infection with zwf mutant Salmonella causes a prompt restoration of virulence, while inhibition of inducible nitric oxide synthase results in delayed lethality. These observations suggest that G6PD-dependent bacterial antioxidant defenses play an important pathogenic role during early salmonellosis and additionally may help to antagonize NO-dependent antimicrobial mechanisms later in the course of infection.
Lundberg
B E
BE
Department of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA.
Wolf
R E
RE
Dinauer
M C
MC
Xu
Y
Y
Fang
F C
FC
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism / Q000502:physiology*; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009584:Nitrogen / Q000378:metabolism*; D009603:Nitroso Compounds / Q000494:pharmacology; D010586:Phagocytes / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D026422:S-Nitrosoglutathione; D012486:Salmonella typhimurium / Q000187:drug effects / Q000201:enzymology* / Q000472:pathogenicity*; D014774:Virulence
D000975:Antioxidants; D009603:Nitroso Compounds; D017382:Reactive Oxygen Species; D026422:S-Nitrosoglutathione; D006861:Hydrogen Peroxide; D005954:Glucosephosphate Dehydrogenase; D005978:Glutathione; D009584:Nitrogen