A HECT Ubiquitin-Protein Ligase as a Novel Candidate Gene for Altered Quinine and Quinidine Responses in

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Quinine, a natural product from cinchona bark, has been used in the treatment of malaria for centuries. Unfortunately, a progressive loss in responsiveness of the human malaria parasite Plasmodium falciparum to quinine has been observed, particularly in Southeast Asia, where cases of quinine treatment failure regularly occur. To better understand how P. falciparum defends itself against the cytotoxic activity of quinine, we have conducted comparative linkage analyses in the F1 progeny of a genetic cross where we assessed the susceptibility and the amount of intracellular accumulation of quinine and of its stereoisomer quinidine. These data identified a novel candidate gene encoding a HECT ubiquitin-protein ligase that might contribute to altered quinine responsiveness. The identification of this novel gene might improve the surveillance of quinine-resistant malaria parasites in the field and aid the preservation of this valuable antimalarial drug.

Vyšlo v časopise: A HECT Ubiquitin-Protein Ligase as a Novel Candidate Gene for Altered Quinine and Quinidine Responses in. PLoS Genet 10(5): e32767. doi:10.1371/journal.pgen.1004382
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004382

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