Fig. 2: Role of AcAS in the mode of action of MMV693183.

a Drug-sensitivity profiles with asexual (upper panel) or sexual (lower panel) blood-stage parasites without a mutation (NF54-HGL) or with a T648M or T627A mutation in AcAS. An MMV693183-selected resistant parasite line (dT648M) was tested in one experiment with two technical replicates and the CRISPR-engineered parasites (cT648M and cT627A) were tested in three independent experiments (two technical replicates per experiment). The average value for mean parasite density relative to controls ± SEM are shown. b Concentration-dependent changes in levels of endogenous metabolites (upper panel) and pantothenamide antimetabolites (lower panel) upon treating P. falciparum-infected RBCs with MMV693183 or no drug. 3D7 parasites were synchronized at the trophozoite stage and treated with increasing concentrations of compound for 2.5 h and (anti)metabolites were quantified in two independent experiments with three technical replicates. Untreated parasites represent the background levels of MMV693183 metabolites. CoA could not be identified in the second experiment, therefore, only data from the first experiment are shown for the CoA level. The fold change is determined relative to no drug control (0 nM). Pan: pantothenate; 4’P-Pan: 4’-phosphopantothenate; Ac-CoA: acetyl-CoA. c Drug-sensitivity assays on conditional knockdown parasites of AcAS (upper panel) or a control target (lower panel) on asexual blood stages at low or high aTc were tested in three independent experiments (N = 3). The graphs show parasite survival based on a luminescence readout compared to controls ± SEM. aTc, anhydrotetracycline. Source data are provided as Source Data file.