IDENTIFICATION OF A CHLOROQUINE IMPORTER IN PLASMODIUM-FALCIPARUM - DIFFERENCE IN IMPORT KINETICS ARE GENETICALLY LINKED WITH THE CHLOROQUINE-RESISTANT PHENOTYPE

We demonstrate that uptake of the antimalarial drug chloroquine is tem perature dependent, saturable, and inhibitable in Plasmodiun falciparu m. These features are indicative of carrier mediated transport and sug gest that a P. falciparum-encoded protein facilitates chloroquine impo rt. Although both chloroquine-resistant and susceptible parasite isola tes exhibit facilitated chloroquine uptake, the kinetics differ. Chlor oquine-resistant parasite isolates consistently have an import mechani sm with a lower transport activity and a reduced affinity for chloroqu ine. These differences in uptake kinetics are linked with chloroquine resistance in a genetic cross. These data suggest that changes in chlo roquine import kinetics constitute a minimal and necessary event in th e generation of the resistant phenotype. Competitive inhibition of chl oroquine uptake by amiloride derivatives further suggests that chloroq uine import is mediated by a plasmodial Na+/H+ exchanger.