PfCRT and its role in antimalarial drug resistance.

PfCRT and its role in antimalarial drug resistance.
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DOI:
10.1016/j.pt.2012.08.002
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发表时间:
2012-11
影响因子:
9.6
通讯作者:
Fidock DA
Fidock DA
中科院分区:
医学1区
文献类型:
--
作者:
Ecker A;Lehane AM;Clain J;Fidock DA

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恶性疟原虫对氯喹(以前的金标准抗疟药物)的耐药性主要由“氯喹耐药转运体”(PfCRT)的突变形式介导。这些突变赋予PfCRT从细胞内消化液泡(药物作用部位)外排氯喹的能力。最近的研究表明,PfCRT变异也可以影响寄生虫的适应性,保护未成熟的配子体免受氯喹的作用,并改变恶性疟原虫对当前一线治疗的敏感性。这些结果强调了在筛选可能导致新的多药耐药表型的新型pfcrt等位基因时需要保持警惕。
Plasmodium falciparum resistance to chloroquine, the former gold standard antimalarial drug, is mediated primarily by mutant forms of the ‘Chloroquine Resistance Transporter’ (PfCRT). These mutations impart upon PfCRT the ability to efflux chloroquine from the intracellular digestive vacuole, the site of drug action. Recent studies reveal that PfCRT variants can also affect parasite fitness, protect immature gametocytes against chloroquine action, and alter P. falciparum susceptibility to current first-line therapies. These results highlight the need to be vigilant in screening for the appearance of novel pfcrt alleles that could contribute to new multi-drug resistance phenotypes.
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