Genetic validation of Trypanosoma brucei glutathione synthetase as an essential enzyme.

ABSTRACT: Human African trypanosomiasis (HAT) is a debilitating and fatal vector-borne disease. Polyamine biosynthesis is the target of one of the key drugs (eflornithine) used for the treatment of late-stage disease, suggesting that the pathway might be exploited for the identification of additional drug targets. The polyamine spermidine is required in trypanosomatid parasites for formation of a unique redox cofactor termed trypanothione, which is formed from the conjugation of glutathione to spermidine. Here we characterize recombinant Trypanosoma brucei glutathione synthetase (TbGS) and show that depletion of TbGS in blood-form parasites using a regulated knockout strategy leads to loss of trypanothione and to cell death as quantified by fluorescence-activated cell sorter (FACS) analysis. These d

SUBMITTER: Pratt C 

PROVIDER: S-EPMC4060477 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature