antimalarial exposure delays plasmodium falciparum intra-erythrocytic cycle and drives drug transporter genes expression抗疟曝光延迟恶性疟原虫intra-erythrocytic周期和驱动器药物转运体基因表达.pdf

Antimalarial Exposure Delays Plasmodium falciparum Intra-Erythrocytic Cycle and Drives Drug Transporter Genes Expression 1,2 1,2 1 3 ¨ 1 Maria Isabel Veiga *, Pedro Eduardo Ferreira , Berit Aydin Schmidt , Ulf Ribacke , Anders Bjorkman , 4,5 ´ 1,2,6 Ales Tichopad , Jose Pedro Gil 1 Malaria Research Lab, Department of Medicine, Karolinska Institutet, Stockholm, Sweden, 2 Drug Resistance and Pharmacogenetics Group, Institute of Biotechnology and Bioengineering, Centre of Molecular and Structural Biomedicine, University of Algarve, Faro, Portugal, 3 Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden, 4 Institute of Biotechnology AS CR, Prague, Czech Republic, 5 Physiology Weihenstephan, Technical University Munich, Freising- Weihenstephan, Germany, 6 Laboratory of Molecular Anthropology and Health, Department of Anthropology, Binghamton University, Binghamton, New York, United States of America Abstract Background: Multi-drug resistant Plasmodium falciparum is a major obstacle to malaria control and is emerging as a complex phenomenon. Mechanisms of drug evasion based on the intracellular extrusion of the drug and/or modification of target proteins have been described. However, cellular mechanisms related with metabolic activity have also been seen in eukaryotic systems, e.g. cancer cells. Recent observations suggest that such mechanism may occur in P. falciparum. Methodology/Principal Findings: We therefore investigated the effect of mefloquine exposure on the cell cycle of three P. falciparum clones (3D7, FCB, W2) with different drug susceptibilities, while investigating in parallel the