PLASMODIUM-FALCIPARUM - AMPLIFICATION AND OVEREXPRESSION OF PFMDR1 ISNOT NECESSARY FOR INCREASED MEFLOQUINE RESISTANCE

Amplification and overexpression of the pfmdr1 gene has been associate d with mefloquine resistance in Plasmodium falciparum. We have selecte d for parasites more resistant to mefloquine from P. falciparum FAC8, a clone that has three copies of pfmdr1. The parasite lines derived fr om this selection were up to threefold more resistant to mefloquine. T he mefloquine-selected parasites were also more resistant to quinine a nd halofantrine, suggesting a multidrug resistance phenotype. In contr ast to previous findings, the selection of P. falciparum FAGS on meflo quine did not alter the copy number or the level of expression of pfmd r1. Sequence analysis of pfmdr1 from the selected lines showed no chan ge in the amino acids. These results show that alterations in pfmdr1 a re not involved in mediating the increased mefloquine resistance obser ved in this clone. (C) 1996 Academic Press, Inc.