Glutathione disulfide and S-nitrosoglutathione detoxification by Mycobacterium tuberculosis thioredoxin system.
Mycobacterium tuberculosis resides within alveolar macrophages. These phagocytes produce reactive nitrogen and oxygen intermediates to combat the invading pathogens. The macrophage glutathione (GSH) pool reduces nitric oxide (NO) to S-nitrosoglutathione (GSNO). Both glutathione disulfide (GSSG) and GSNO possess mycobactericidal activities in vitro. In this study we demonstrate that M. tuberculosis thioredoxin system, comprises of thioredoxin reductase B2 and thioredoxin C reduces the oxidized form of the intracellular mycothiol (MSSM) and is able to efficiently reduce GSSG and GSNO in vitro. Our study suggests that the thioredoxin system provide a general reduction mechanism to cope with oxidative stress associated with the microbe's metabolism as well as to detoxify xenobiotics produced by the host.
Attarian
Rodgoun
R
Department of Medicine, Division of Infectious Diseases, University of British Columbia, Vancouver, British Columbia, Canada V5Z 3J5.
Bennie
Chelsea
C
Bach
Horacio
H
Av-Gay
Yossef
Y
D019803:Glutathione Disulfide / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D010084:Oxidation-Reduction; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D026422:S-Nitrosoglutathione / Q000378:metabolism*; D013880:Thioredoxin-Disulfide Reductase / Q000235:genetics / Q000378:metabolism*; D013879:Thioredoxins / Q000378:metabolism*
D011994:Recombinant Proteins; D013879:Thioredoxins; D026422:S-Nitrosoglutathione; D013880:Thioredoxin-Disulfide Reductase; D019803:Glutathione Disulfide