Figure 4

Responses of pfcrt and pfmdr1 allelic exchange parasites to dihydroartemisinin + lidocaine (DHA + LID) combination.

(a) Sum of fractional inhibitory concentrations (ΣFIC) of pfcrt allelic exchanged parasites in response to DHA + LID combination analyzed using isobolograms. The GCO3 parasite has a wild type pfcrt. C1^GCO3 and C2^GCO3 are both allelic exchange control parasite lines retaining the wild-type pfcrt locus and C4^Dd2 and C6^7G8 are allelic exchange parasites with pfcrt replaced with the Dd2 or 7G8 allele, respectively. (b) Sum of fractional inhibitory concentrations (ΣFIC) of pfmdr1 allelic exchanged parasites in response to DHA + LID combination analyzed using isobolograms. Indicated are the amino acids encoded at position 1034, 1042 and 1246. GCO3 and 3BA6 have the mutant SDD PfMDR1 allele; FCB has the wild type SND PfMDR1 allele. Shown for isobologram assays are the Mean ΣFIC ± SD, with at least three independent experiments. Note 3BA6^CDY was only significantly different from 3BA6, not the 3BA6^SDD allelic control parasite. Because both 3BA6 and 3BA6^SDD had the same SDD PfMDR1 allele, the lack of significance for both control parasites and the 3BA6^CDY modified line indicated that transgenic modification of the line was confounding the phenotype, precluding a clear conclusion about these comparisons; t-test, *P < 0.05; **P < 0.01.