Control of Mycobacterium tuberculosis Infection by Glutathione

Nancy   D.   Connell; Vishwanath      Venketaraman

doi:10.2174/157489109789318541

Abstract

Tuberculosis is the most prevalent infectious disease in the world. It is also believed that in developing countries, as many as 40 to 80% of individuals with AIDS are at risk of developing tuberculosis. In recent years there has been a significant increase in the incidence of tuberculosis due to the emergence of multi-drug resistant strains of Mycobacterium tuberculosis and due to increased numbers of highly susceptible immuno-compromised individuals arising from the AIDS pandemic. Extreme drug resistant tuberculosis raises the possibility that the current tuberculosis epidemic of mostly drug-susceptible tuberculosis will be replaced with a form of tuberculosis with severely restricted treatment options. This phenomenon would jeopardize the progress made in recent years to control tuberculosis globally and would also put at risk the plans to progress towards universal access to HIV prevention and treatment. Patients with extreme drug-resistant tuberculosis would have to be managed in the same way as tuberculosis patients before the antibiotic era. No new anti-tuberculosis drugs have been brought into the clinic in the past 40 years. Immuno-adjunctive therapy appears to be promising in improving outcome of clinical control of refractory mycobacterial infections, including multi-drug resistant tuberculosis and Mycobacterium avium complex infection. The tripeptide, glutathione protects all cells against oxidizing agents, free radicals and reactive oxygen intermediates, either directly or through enzymatic action of glutathione peroxidases and glutathione-transferases. This review article is a compilation of our major research findings on the innate immune responses against Mycobacterium tuberculosis infection. We discuss in detail both the direct antimycobacterial effects as well as the immune enhancing effects of glutathione leading to the inhibition of growth of Mycobacterium tuberculosis. The article presents some new promising patents related to the control of Mycobacterium tuberculosis infection.

Keywords: Tuberculosis, innate immunity, macrophages, natural killer cells, cytokines, glutathione

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