Chloroquine resistance not linked to mdr-like genes in a Plasmodium falciparum cross

CHLOROQUINE is thought to act against falciparum malaria by accumulating in the acid vesicles of the parasite and interfering with their function 1–4 . Parasites resistant to chloroquine expel the drug rapidly in an unaltered form, thereby reducing levels of accumulation in the vesicles 5 . The discovery that verapamil partially reverses chloroquine resistance in vitro 6 led to the proposal that efflux may involve an ATP-driven P-glycoprotein pump similar to that in mammalian multidrug-resistant ( mdr ) tumor cell lines. Indeed, Plasmodium falciparum contains at least two mdr -like genes 7,8 , one of which has been suggested to confer the chloroquine resistant (CQR) phenotype 7,9,10 . To determine if either of these genes is linked to chloroquine resistance, we performed a genetic cross between CQR and chloroquine-susceptible (CQS) clones of P. falciparum . Examination of 16 independent recombinant progeny indicated that the rapid efflux phenotype is controlled by a single gene or a closely linked group of genes. But, there was no linkage between the rapid efflux, CQR phenotype and either of the mdr -like P. falciparum genes or amplification of those genes. These data indicate that the genetic locus governing chloroquine efflux and resistance is independent of the known mdr -like genes.