Characterization of a Glutathione Metabolic Mutant ofMycobacterium tuberculosisand Its Resistance to Glutathione and Nitrosoglutathione
Open Access
- 15 February 2006
- journal article
- Published by American Society for Microbiology in Journal of Bacteriology
- Vol. 188 (4), 1364-1372
- https://doi.org/10.1128/jb.188.4.1364-1372.2006
Abstract
Glutathione is a tripeptide and antioxidant, synthesized at high levels by cells during the production of reactive oxygen and nitrogen intermediates. Glutathione also serves as a carrier molecule for nitric oxide in the form ofS-nitrosoglutathione. Previous studies from this laboratory have shown that glutathione andS-nitrosoglutathione are directly toxic to mycobacteria. Glutathione is not transported into the cells as a tripeptide. Extracellular glutathione is converted to a dipeptide due to the action of transpeptidase, and the dipeptide is then transported into the bacterial cells. The processing of glutathione andS-nitrosoglutathione is brought about by the action of the enzyme γ-glutamyl transpeptidase. The function of γ-glutamyl transpeptidase is to cleave glutathione andS-nitrosoglutathione to the dipeptide (Cys-Gly), which is then transported into the bacterium by the multicomponent ABC transporter dipeptide permease. We have created a mutant strain ofMycobacterium tuberculosislacking this metabolic enzyme. We investigated the sensitivity of this strain to glutathione andS-nitrosoglutathione compared to that of the wild-type bacteria. In addition, we examined the role of glutathione and/orS-nitrosoglutathione in controlling the growth of intracellularM. tuberculosisinside mouse macrophages.Keywords
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