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Defining the role of PfCRT in Plasmodium falciparum chloroquine resistance
Author(s) -
Bray Patrick G.,
Martin Rowena E.,
Tilley Leann,
Ward Stephen A.,
Kirk Kiaran,
Fidock David A.
Publication year - 2005
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2005.04556.x
Subject(s) - biology , plasmodium falciparum , chloroquine , efflux , vacuole , transporter , apicomplexa , virology , malaria , drug resistance , membrane transport protein , protozoa , gene , genetics , immunology , cytoplasm
Summary Recent studies have highlighted the importance of a parasite protein referred to as the chloroquine resistance transporter (PfCRT) in the molecular basis of Plasmodium falciparum resistance to the quinoline antimalarials. PfCRT, an integral membrane protein with 10 predicted transmembrane domains, is a member of the drug/metabolite transporter superfamily and is located on the membrane of the intra‐erythrocytic parasite's digestive vacuole. Specific polymorphisms in PfCRT are tightly correlated with chloroquine resistance. Transfection studies have now proven that pfcrt mutations confer verapamil‐reversible chloroquine resistance in vitro and reveal their important role in resistance to quinine. Available evidence is consistent with the view that PfCRT functions as a transporter directly mediating the efflux of chloroquine from the digestive vacuole.