PfCRT 及其在抗疟药物耐药性中的作用。
PfCRT and its role in antimalarial drug resistance.
机构信息
Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
出版信息
Trends Parasitol. 2012 Nov;28(11):504-14. doi: 10.1016/j.pt.2012.08.002. Epub 2012 Sep 25.
Abstract
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.
摘要
恶性疟原虫对氯喹（以前的抗疟标准药物）的耐药性主要由氯喹耐药转运蛋白（PfCRT）的突变形式介导。这些突变赋予 PfCRT 将氯喹从细胞内消化液泡中排出的能力，而这正是药物作用的部位。最近的研究表明，PfCRT 变体还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方法的敏感性。这些结果强调了需要警惕筛查新的 pfcrt 等位基因的出现，这些等位基因可能导致新的多药耐药表型。
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