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Homocysteine antagonism of nitric oxide-related cytostasis in Salmonella typhimurium.
Title | Homocysteine antagonism of nitric oxide-related cytostasis in Salmonella typhimurium. |
Publication Type | Journal Article |
Year of Publication | 1996 |
Authors | De Groote, MA, Testerman, T, Xu, Y, Stauffer, G, Fang, FC |
Journal | Science |
Volume | 272 |
Issue | 5260 |
Pagination | 414-7 |
Date Published | 1996 Apr 19 |
ISSN | 0036-8075 |
Keywords | Animals, Aspartokinase Homoserine Dehydrogenase, Base Sequence, Drug Resistance, Microbial, Female, Glutathione, Homocysteine, Mercaptoethanol, Mice, Mice, Inbred C3H, Microbial Sensitivity Tests, Molecular Sequence Data, Mutagenesis, Insertional, Nitric Oxide, Nitroso Compounds, S-Nitrosoglutathione, S-Nitrosothiols, Salmonella Infections, Animal, Salmonella typhimurium, Virulence |
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. |
Alternate Journal | Science |
PubMed ID | 8602531 |
Grant List | AI32463 / AI / NIAID NIH HHS / United States |