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Infection and Immunity, April 2003, p. 1864-1871, Vol. 71, No. 4
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.4.1864-1871.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Role of Glutathione in Macrophage Control of Mycobacteria

Vishwanath Venketaraman,1,2,3 Yaswant K. Dayaram,1,2,3 Amol G. Amin,1,2,3 Richard Ngo,1 Renee M. Green,1 Meliza T. Talaue,1,2,3 Jessica Mann,1,2,3 and Nancy D. Connell1,2,3*

Department of Microbiology and Molecular Genetics,1 New Jersey Medical School National Tuberculosis Center ,2 Center for Emerging and Re-emerging Pathogens, UMDNJ-New Jersey Medical School, Newark, New Jersey 071033

Received 3 July 2002/ Returned for modification 8 October 2002/ Accepted 14 January 2003

Reactive oxygen and nitrogen intermediates are important antimicrobial defense mechanisms of macrophages and other phagocytic cells. While reactive nitrogen intermediates have been shown to play an important role in tuberculosis control in the murine system, their role in human disease is not clearly established. Glutathione, a tripeptide and antioxidant, is synthesized at high levels by cells during reactive oxygen intermediate and nitrogen intermediate production. Glutathione has been recently shown to play an important role in apoptosis and to regulate antigen-presenting-cell functions. Glutathione also serves as a carrier molecule for nitric oxide, in the form of S-nitrosoglutathione. Previous work from this laboratory has shown that glutathione and S-nitrosoglutathione are directly toxic to mycobacteria. A mutant strain of Mycobacterium bovis BCG, defective in the transport of small peptides such as glutathione, is resistant to the toxic effect of glutathione and S-nitrosoglutathione. Using the peptide transport mutant as a tool, we investigated the role of glutathione and S-nitrosoglutathione in animal and human macrophages in controlling intracellular mycobacterial growth.

* Corresponding author. Mailing address: Department of Microbiology and Molecular Genetics, UMDNJ-NJMS, International Center for Public Health, 225 Warren St., Newark, NJ 07103. Phone: (973) 972-4483, ext. 28963. Fax: (973) 972-3644. E-mail: connell{at}umdnj.edu.

Editor: S. H. E. Kaufmann

Infection and Immunity, April 2003, p. 1864-1871, Vol. 71, No. 4
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.4.1864-1871.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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