Mefloquine Exposure Induces Cell Cycle Delay and Reveals Stage-Specific Expression of the pfmdr1 Gene

摘要: Drug-resistant Plasmodium falciparum malaria is a major public health problem. An elevated pfmdr1 gene copy number (CN) known to decrease parasite sensitivity the commonly used antimalarial mefloquine (MFQ). To understand relationship between CN and resistance, we evaluated transcript levels in three P. strains with different CNs presence absence of MFQ. Parasite multiple copies exhibited higher relative than single-copy parasites, MFQ induced expression above without treatment all evaluated. Concomitant morphology analyses sampled cultures revealed that synchronized ring-stage parasites delay maturation through intraerythrocytic cycle. peaks ring stage, could be causing increased transcription by delaying maturation. However, pretreatment did not affect artemisinin vitro half-maximal inhibitory concentration (IC(50)). These results suggest MFQ-induced increases are direct result at stage but this change does activity artemisinin.