STAGE-SPECIFIC TRANSCRIPTS OF THE PLASMODIUM-FALCIPARUM-PFMDR-1 GENE

Genes have been identified in Plasmodium falciparum which belong to the ATP-binding cassette superfamily of transport systems based upon sequence and structural homology. One of these genes, the pfmdr1 gene, is homologous to the mammalian mdr1 gene, which encodes the P-glycoprotein product. Strong phenotypic data suggests the involvement of a P-glycoprotein-like molecule in the mediation of drug resistance in P.falciparum. The goal of this work was to characterize the expression of the pfmdr1 messenger RNA: both the stage specific expression and the level of expression in mefloquine sensitive or resistant parasites. We identified two messenger RNAs homologous to this gene, one of 8.5 kb expressed in ring and trophozoite stages, and a second messenger RNA of 7.5 kb expressed only in trophozoites. Previously we had reported an increased expression of messenger RNA for pfmdr1 in a mefloquine-resistant clone. Here we extend this and demonstrate that overexpression of the pfmdr1 gene is consistent with the mefloquine resistance phenotype in a panel of recent isolates from Thailand.