Publication Date:
1996-04-19
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉De Groote, M A -- Testerman, T -- Xu, Y -- Stauffer, G -- Fang, F C -- AI32463/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1996 Apr 19;272(5260):414-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8602531" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Aspartokinase Homoserine Dehydrogenase/genetics/*metabolism
;
Base Sequence
;
Drug Resistance, Microbial
;
Female
;
Glutathione/analogs & derivatives/pharmacology
;
Homocysteine/metabolism/pharmacology/*physiology
;
*Mercaptoethanol
;
Mice
;
Mice, Inbred C3H
;
Microbial Sensitivity Tests
;
Molecular Sequence Data
;
Mutagenesis, Insertional
;
Nitric Oxide/*antagonists & inhibitors/metabolism
;
Nitroso Compounds/pharmacology
;
S-Nitrosoglutathione
;
*S-Nitrosothiols
;
Salmonella Infections, Animal/microbiology
;
Salmonella typhimurium/cytology/drug effects/pathogenicity/*physiology
;
Virulence
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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