Volume 51, Issue 5
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Stepwise selection for increased mefloquine resistance in a line of in vitro resulted in increased resistance to halofantrine and quinine, increased sensitivity to chloroquine, and amplification and overexpression of the P-glycoprotein gene homolog (). A point mutation (tyrosine to phenylalanine) noted at amino acid 86 in in the mefloquine-resistant line W2mef was amplified in more resistant lines derived from it by in vitro selection pressure with mefloquine. Conversely, lines selected for increased chloroquine resistance exhibited a revertant phenotype that was sensitive to mefloquine and halofantrine. These lines also demonstrated increased sensitivity to quinine, loss of amplification of , loss of the mefloquine/halofantrine phenylalanine-86 mutation, and selection for a tyrosine-86 mutation previously associated with chloroquine resistance. These findings provide strong evidence for mediating cross-resistance to halofantrine and mefloquine in in vitro.


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