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Volume 272, Number 5, Issue of January 31, 1997 pp. 2652-2658
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

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Identification of a Chloroquine Importer in Plasmodium falciparum
DIFFERENCES IN IMPORT KINETICS ARE GENETICALLY LINKED WITH THE CHLOROQUINE-RESISTANT PHENOTYPE

(Received for publication, June 28, 1996, and in revised form, August 19, 1996)

From the Zentrum für Infektionsforschung der Universität Würzburg, Röntgenring 11, D-97070 Würzburg, Federal Republic of Germany

We demonstrate that uptake of the antimalarial drug chloroquine is temperature-dependent, saturable, and inhibitable in Plasmodium falciparum. These features are indicative of carrier-mediated transport and suggest that a P. falciparum-encoded protein facilitates chloroquine import. Although both chloroquine-resistant and susceptible parasite isolates exhibit facilitated chloroquine uptake, the kinetics differ. Chloroquine-resistant parasite isolates consistently have an import mechanism with a lower transport activity and a reduced affinity for chloroquine. These differences in uptake kinetics are linked with chloroquine resistance in a genetic cross. These data suggest that changes in chloroquine import kinetics constitute a minimal and necessary event in the generation of the resistant phenotype. Competitive inhibition of chloroquine uptake by amiloride derivatives further suggests that chloroquine import is mediated by a plasmodial Na⁺/H⁺ exchanger.

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