1. Homocysteine antagonism of nitric oxide-related cytostasis in Salmonella typhimurium.
- Author
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De Groote MA, Testerman T, Xu Y, Stauffer G, and Fang FC
- Subjects
- Animals, Aspartokinase Homoserine Dehydrogenase genetics, Base Sequence, Drug Resistance, Microbial, Female, Glutathione analogs & derivatives, Glutathione pharmacology, Homocysteine metabolism, Homocysteine pharmacology, Mice, Mice, Inbred C3H, Microbial Sensitivity Tests, Molecular Sequence Data, Mutagenesis, Insertional, Nitric Oxide metabolism, Nitroso Compounds pharmacology, S-Nitrosoglutathione, Salmonella Infections, Animal microbiology, Salmonella typhimurium cytology, Salmonella typhimurium drug effects, Salmonella typhimurium pathogenicity, Virulence, Aspartokinase Homoserine Dehydrogenase metabolism, Homocysteine physiology, Mercaptoethanol, Nitric Oxide antagonists & inhibitors, S-Nitrosothiols, Salmonella typhimurium physiology
- Abstract
Nitric oxide (NO) is associated with broad-spectrum antimicrobial activity of particular importance in infections caused by intracellular pathogens. An insertion mutation in the metL gene of Salmonella typhimurium conferred specific hypersusceptibility to S-nitrosothiol NO-donor compounds and attenuated virulence of the organism in mice. The metL gene product catalyzes two proximal metabolic steps required for homocysteine biosynthesis. S-Nitrosothiol resistance was restored by exogenous homocysteine or introduction of the metL gene on a plasmid. Measurement of expression of the homocysteine-sensitive metH gene indicated that S-nitrosothiols may directly deplete intracellular homocysteine. Homocysteine may act as an endogenous NO antagonist in diverse processes including infection, atherosclerosis, and neurologic disease.
- Published
- 1996
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