FIG. 1.

Concentration-response curves describing the in vitro inhibition of growth and protein synthesis in P. falciparum by micrococcin and thiostrepton. Data are the percent reduction values from no drug controls and are means of three determinations. Dashed lines, micrococcin; solid lines, thiostrepton. Incorporation of [³H]hypoxanthine (○) and [³H]leucine (□) was measured at the concentrations of drug shown. For the assays, an in vitro culture of P. falciparum (strains 3D7 and LF4) was diluted in microtiter plates as described previously (7). Micrococcin P (M_r, 1,120 [a kind gift from J. Walker]) and thiostrepton (M_r, 1,660 [Calbiochem]) were dissolved at 100 mM in sterile dimethyl sulfoxide (silylation grade [Pierce]); at the highest concentrations used, the drugs precipitated in the media. Parasites were grown for 48 h in the presence of serial dilutions of thiostrepton or micrococcin, together with drug-free controls. Labeling with [³H]hypoxanthine or [³H]leucine in medium lacking hypoxanthine or leucine, respectively, was as described elsewhere (7). Cells were harvested and lysed, and incorporated radioactivity was estimated. Data shown are for P. falciparum 3D7, but these were similar to data for LF4 (IC₅₀ for growth, 39 nM).