Fig 3. L-[¹⁴C]lactate influx into PfFNT^Gly107Ser mutant parasites and Dd2 parental parasites.

(A) The uptake of L-[¹⁴C]lactate by isolated trophozoite-stage PfFNT^Gly107Ser mutant parasites (white bars) and Dd2 parental parasites (black bars) in the absence of compound (0.4% v/v DMSO; solvent control) and in the presence of the non-specific anion transport inhibitor NPPB (100 μM). The mean distribution ratio (i.e., [intracellular L-[¹⁴C]lactate]/[extracellular L-[¹⁴C]lactate]) and SEM from nine (parent) or seven (mutant) independent experiments for the control, and from three independent experiments for NPPB, are shown. The results of unpaired t-tests are shown; ***P < 0.001. (B-C) The effects of MMV007839 (B) and MMV000972 (C) on L-[¹⁴C]lactate uptake into isolated trophozoite-stage PfFNT^Gly107Ser mutant parasites (white symbols) and Dd2 parental parasites (black symbols). L-[¹⁴C]lactate uptake in the presence of each concentration of MMV compound is expressed as a percentage of that observed when there was no inhibition of transport. The data shown are the average ± SEM from n independent experiments performed on different days, where n was seven for the MMV007839 data with parental parasites, three for the MMV007839 data with PfFNT^Gly107Ser mutant parasites, three for the MMV000972 data with parental parasites, and four for the MMV000972 data with PfFNT^Gly107Ser mutant parasites (with the exception of the lowest concentration, for which there was one less experiment in all cases). In all cases (panels A-C), the experiments were performed at 4°C in pH 6.1 Experimental Saline Solution, and parasites were preincubated with the compound (at the concentration indicated) or DMSO (0.4% v/v; solvent control) for 1 min prior to the addition of L-[¹⁴C]lactate (1.3 μM). The concentrations of compound and DMSO after the addition of L-[¹⁴C]lactate were the same as those present during the preincubation. The uptake of L-[¹⁴C]lactate was measured over 20 s.