XB-ART-40264
Science
2009 Sep 25;3255948:1680-2. doi: 10.1126/science.1175667.
Show Gene links
Show Anatomy links
Chloroquine transport via the malaria parasite's chloroquine resistance transporter.
???displayArticle.abstract???
The emergence and spread of chloroquine-resistant Plasmodium falciparum malaria parasites has been a disaster for world health. Resistance is conferred by mutations in the Chloroquine Resistance Transporter (PfCRT), an integral membrane protein localized to the parasite's internal digestive vacuole. These mutations result in a marked reduction in the accumulation of chloroquine (CQ) by the parasite. However, the mechanism by which this occurs is unclear. We expressed both wild-type and resistant forms of PfCRT at the surface of Xenopus laevis oocytes. The resistant form of PfCRT transported CQ, whereas the wild-type protein did not. CQ transport via the mutant PfCRT was inhibited by CQ analogs and by the resistance-reverser verapamil. Thus, CQ resistance is due to direct transport of the drug via mutant PfCRT.
???displayArticle.pubmedLink??? 19779197
???displayArticle.link??? Science