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Science 19 April 1996:
Vol. 272. no. 5260, pp. 414 - 417
DOI: 10.1126/science.272.5260.414
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Reports

Homocysteine Antagonism of Nitric Oxide-Related Cytostasis in Salmonella typhimurium

Mary Ann De Groote, Traci Testerman, Yisheng Xu, George Stauffer, Ferric C. Fang *

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.

M. A. De Groote, T. Testerman, Y. Xu, F. C. Fang, Departments of Medicine, Pathology, and Microbiology, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
G. Stauffer, Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.
* To whom correspondence should be addressed.


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