A HECT ubiquitin-protein ligase as a novel candidate gene for altered quinine and quinidine responses in Plasmodium falciparum.

摘要: The emerging resistance to quinine jeopardizes the efficacy of a drug that has been used in treatment malaria for several centuries. To identify factors contributing differential responses human parasite Plasmodium falciparum, we have conducted comparative quantitative trait locus analyses on susceptibility and also its stereoisomer quinidine, initial steady-state intracellular accumulation levels F1 progeny genetic cross. These data, together with screens field isolates laboratory strains associated quinidine mutated pfcrt, segment chromosome 13, novel candidate gene, termed MAL7P1.19 (encoding HECT ubiquitin ligase). Despite strong likelihood association, episomal transfections demonstrated role ubiquitin-protein ligase sensitivity only subset backgrounds, here changes IC50 values were moderate (approximately 2-fold). data show responsiveness is complex multiple alleles playing more experiments are needed unravel factors.