Chloroquine transport via the malaria parasite's chloroquine resistance transporter

Rowena E. Martin, Rosa V. Marchetti, Anna I. Cowan, Susan M. Howitt, Stefan Bröer, Kiaran Kirk

    Research output: Contribution to journalArticlepeer-review

    252 Citations (Scopus)

    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 (CO) 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.

    Original languageEnglish
    Pages (from-to)1680-1682
    Number of pages3
    JournalScience
    Volume325
    Issue number5948
    DOIs
    Publication statusPublished - 2009

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