Fig. 4: Evolution of resistance to an “irresistible” compound.
From: Generation of a mutator parasite to drive resistome discovery in Plasmodium falciparum
A Selection scheme showing inability to evolve resistance to MMV665794 with Dd2-WT, but successful isolation of resistance with Dd2-Polδ. Upper panel: Dd2-WT exposed to 1 × IC50 (95 nM) for 60 days. Lower panel: Dd2-Polδ selection pressure was ramped to 2 × IC50 (190 nM), with recrudescence observed after 60 days in 3 independent flasks, but only 2 of 3 flasks could stably grow under drug pressure. Recrudescent parasites were further challenged with 3× and 4 × IC50 but failed to survive. B Dose-response curves of MMV665794 for parental lines and the two resistant lines (C1-2) that were able to survive under 2 × IC50 pressure. Shown is a representative assay (two technical replicates, error bars showing SD), with IC50 values represented as mean values +/−SD derived from the following biological replicates (DNA-Polδ, n = 7; Polδ-R1, n = 5; Polδ-R2, n = 5). Source data are provided as a Source Data file.
