Patzewitz, E.-M., Wong, E.H. and Muller, S. (2012) Dissecting the role of glutathione biosynthesis in Plasmodium falciparum. Molecular Microbiology, 83(2), pp. 304-318. (doi: 10.1111/j.1365-2958.2011.07933.x)
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Publisher's URL: http://dx.doi.org/10.1111/j.1365-2958.2011.07933.x
Abstract
Glutathione (γ-glutamylcysteinyl-glycine, GSH) has vital functions as thiol redox buffer and cofactor of antioxidant and detoxification enzymes. Plasmodium falciparum possesses a functional GSH biosynthesis pathway and contains mM concentrations of the tripeptide. It was impossible to delete in P. falciparum the genes encoding γ-glutamylcysteine synthetase (γGCS) or glutathione synthetase (GS), the two enzymes synthesizing GSH, although both gene loci were not refractory to recombination. Our data show that the parasites cannot compensate for the loss of GSH biosynthesis via GSH uptake. This suggests an important if not essential function of GSH biosynthesis pathway for the parasites. Treatment with the irreversible inhibitor of γGCS L-buthionine sulfoximine (BSO) reduced intracellular GSH levels in P. falciparum and was lethal for their intra-erythrocytic development, corroborating the suggestion that GSH biosynthesis is important for parasite survival. Episomal expression of γgcs in P. falciparum increased tolerance to BSO attributable to increased levels of γGCS. Concomitantly expression of glutathione reductase was reduced leading to an increased GSH efflux. Together these data indicate that GSH levels are tightly regulated by a functional GSH biosynthesis and the reduction of GSSG.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Muller, Professor Sylke and Patzewitz, Ms Eva-Maria and Wong, Dr Eleanor |
| Authors: | Patzewitz, E.-M., Wong, E.H., and Muller, S. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Molecular Microbiology |
| ISSN: | 0950-382X |
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