疟原虫氯喹抗性转运蛋白（PfCRT）是一种通道还是载体？两种相互竞争的模型解释恶性疟原虫对氯喹的抗性。

Is PfCRT a channel or a carrier? Two competing models explaining chloroquine resistance in Plasmodium falciparum.

作者信息

Sanchez Cecilia P, Stein Wilfred D, Lanzer Michael

机构信息

Hygiene Institut, Abteilung Parasitologie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany.

出版信息

Trends Parasitol. 2007 Jul;23(7):332-9. doi: 10.1016/j.pt.2007.04.013. Epub 2007 May 10.

DOI:10.1016/j.pt.2007.04.013

PMID:17493873

Abstract

Chloroquine (CQ), an antimalarial drug with a long history, now frequently fails in the field owing to the rapid spread of resistant Plasmodium falciparum strains. CQ resistance is linked to a K76T mutation in PfCRT, a membrane-located food vacuolar protein and member of the drug-metabolite transporter superfamily, but there is as yet no agreed mechanism of how mutated PfCRT brings about CQ resistance. Current models suggest that mutated PfCRT acts either as a channel or a transporter of CQ, enabling CQ to leave the digestive food vacuole of the parasite, in which the CQ accumulates. Here, we review the pros and cons of the carrier and transporter models in light of recent developments in the field.

摘要

氯喹（CQ）是一种历史悠久的抗疟药物，由于恶性疟原虫耐药菌株的迅速传播，目前在实际应用中常常失效。CQ耐药性与PfCRT中的K76T突变有关，PfCRT是一种位于膜上的食物泡蛋白，属于药物代谢物转运蛋白超家族的成员，但目前对于突变的PfCRT如何导致CQ耐药性尚无一致认可的机制。目前的模型表明，突变的PfCRT要么作为CQ的通道，要么作为CQ的转运体，使CQ能够离开寄生虫的消化食物泡，而CQ会在该食物泡中积累。在此，我们根据该领域的最新进展，对载体模型和转运体模型的优缺点进行综述。