PLASMODIUM-FALCIPARUM - THE PFMDR2 PROTEIN IS NOT OVEREXPRESSED IN CHLOROQUINE-RESISTANT ISOLATES OF THE MALARIA PARASITE

We have isolated and sequenced a full-length gene (pfmdr2) that has ho mology to the ABC (ATP-binding cassette)-type transport proteins which includes the mammalian P-glycoproteins, CFTR, and the protein product of the Plasmodium falciparum pfmdr1 gene. The protein encoded by the pfmdr2 gene has 10 hydrophobic domains followed by a region homologous to the nucleotide binding fold of the ABC transport proteins. The pfm dr2 protein also shows homology outside the nucleotide binding fold an d some structural similarity to HMT1, a protein involved in heavy meta l tolerance in Schizosaccharomyces pombe. Antibodies raised to the pfm dr2 protein react with a 110-kDa band and localization by immunofluore scence suggests the protein is expressed over the whole parasite and m ay be located on the plasma membrane of the parasite. Comparison of th e level of expression of the pfmdr2 protein in chloroquine-resistant a nd -sensitive parasites show that it is present at approximately equal levels which is in contrast to previous results that determined the l evel of the pfmdr2 transcript. These results support the evidence that pfmdr2 is not involved in the chloroquine resistance phenotype. (C) 1 994 Academic Press, Inc.