Figure 4: Amplification of a phospholipid-translocating ATPase reduces susceptibility to quinoxaline-containing compounds.

A) Model of PfATP2 lipid flippase. The P4-ATPase is predicted to contain 10 transmembrane segments, with phospholipid translocation from the luminal to cytosolic leaflet of the membrane powered by ATP hydrolysis. B-D) MMV007224-selected clones R1 (pfatp2 CNV) and R2 (pfatp2 CNV and pfqrp1 frameshift) were tested against (B) MMV007224, (C) compound 22, and (D) compound 31. Each dot represents a biological replicate (n=4–5) with mean±SD shown as bar chart, and statistical significance determined by Mann-Whitney U tests (*p<0.05, **p<0.01).