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Journal of Bacteriology, February 2006, p. 1364-1372, Vol. 188, No. 4
0021-9193/06/$08.00+0     doi:10.1128/JB.188.4.1364-1372.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Characterization of a Glutathione Metabolic Mutant of Mycobacterium tuberculosis and Its Resistance to Glutathione and Nitrosoglutathione

Yaswant K. Dayaram,1,3 Meliza T. Talaue,1,3 Nancy D. Connell,1,2,3 and Vishwanath Venketaraman1,2,3*

Department of Microbiology and Molecular Genetics,1 Department of Medicine,2 New Jersey Medical School National Tuberculosis Center, UMDNJ-New Jersey Medical School, Newark, New Jersey 071033

Received 20 July 2005/ Accepted 2 December 2005

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 of S-nitrosoglutathione. Previous studies from this laboratory have shown that glutathione and S-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 and S-nitrosoglutathione is brought about by the action of the enzyme {gamma}-glutamyl transpeptidase. The function of {gamma}-glutamyl transpeptidase is to cleave glutathione and S-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 of Mycobacterium tuberculosis lacking this metabolic enzyme. We investigated the sensitivity of this strain to glutathione and S-nitrosoglutathione compared to that of the wild-type bacteria. In addition, we examined the role of glutathione and/or S-nitrosoglutathione in controlling the growth of intracellular M. tuberculosis inside mouse macrophages.


* Corresponding author. Mailing address: Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, 225 Warren Street, Newark, NJ 07103. Phone: (973) 972-4483, ext. 28963. Fax: (973) 972-8981. E-mail: venketvi{at}umdnj.edu.


Journal of Bacteriology, February 2006, p. 1364-1372, Vol. 188, No. 4
0021-9193/06/$08.00+0     doi:10.1128/JB.188.4.1364-1372.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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