Fig. 5: Knockdown of PfACS10 leads to hypersensitivity to profiled inhibitors.
The conditional knockdown line for PfACS10 was generated with the TetR-aptamer system, similar to the previously generated ACS11cKD and YFPcKD lines40. Viability of the lines was tested by removing anhydrotetracycline (aTc) and measuring parasite proliferation by luminescence of the luciferase reporter gene after 72 h. a Loss of PfACS10 resulted in a complete block of growth, whereas e loss of PfACS11 resulted in a 20% growth reduction. Shown is one biological replicate run in triplicate. Tests for significance used a two-sided unpaired Student’s t test: a: p = 0.0000005, b: p = 0.012. Example of dose response curves for b, f MMV019719, c, g MMV665924, and d, h MMV897615, tested in the presence of high aTc (50 nM), or low aTc (5 nM aTc for ACS10cKD to allow for minimal growth), or no aTc for ACS11cKD and YFPcKD. ACS10cKD parasites in low aTc were significantly more susceptible to all compounds as compared with high aTc. Shown are the average ±SD and the non-linear regression curve fit for one biological assay run in triplicate. In contrast ACS11cKD parasites were less susceptible to the compounds in the absence of aTc, whereas the aTc concentration had no effect on the YFPcKD line. Statistical significances for EC50 are reported in Supplementary Data 1 and source data are provided as a Source Data file. YFP yellow fluorescent protein, aTc anhydrotetracycline.
