Volume 76, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


We investigated the association between the dihydrofolate reductase () and the dihydropteroate synthase () genotype and sensitivity to the antifolates pyrimethamine, WR99210, chlorcycloguanil, sulfadoxine, and dapsone. Drug responses of 32 isolates were assessed in two systems: schizont maturation inhibition and a yeast expression system. The geometric mean of 50% inhibition concentration (IC) values for pyrimethamine, chlorcycloguanil, WR99210, sulfadoxine, and dapsone were 85 ± 88, 784 ± 662, 95 ± 87, 2,424 ± 2,784, and 1,625 ± 1,801 nM, respectively, for the schizont maturation assay. Five different alleles and four alleles were observed: 26 of 32 quadruple mutant alleles of (F57I,L/S58R/T61M/S117T), four triple mutants (S58R/T61M/S117T, K49C/S58R/S117N), and two double mutant isolates (S58R/S117N). All isolates carried 585V. Twenty four isolates carried double mutant (A383G/A553G), six an additional mutation, S382A,C/A383G/A553G, and two a single mutation, A383G. Increasing geometric mean IC values were observed with increased number of mutations from double to quadruple. Results suggest that quadruple mutant alleles confer decreased sensitivity to pyrimethamine but retain sensitivity to WR99210.


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  • Received : 06 Dec 2006
  • Accepted : 11 Feb 2007

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