Fig. 4.

Good agreement between experimental measures and theoretical predictions. Shown are comparisons of experimental (Left) and theoretical (Right) frequencies of resistance for FUS-ERY (A), CPR-AMP (B), and FUS-AMI (C) (blue, dark red, and light red as indicated). Theoretical surfaces for each drug pair were computed based on measured frequencies of resistance to each individual drug, measured epistasis between the drugs (MIC line of the wild type), and fitted cross-resistance (see Materials and Methods). Although the behaviors of the three pairs of drugs in terms of epistasis and cross-resistance are very different, the model accounts remarkably well for the frequencies of resistance and MPC lines (red). (Insets) MSW of “effective drugs” obtained by mixing the two drugs at different proportions; experimental points are plotted with their conservative error bars, and the lines correspond to the model prediction. FUS and ERY can be combined to significantly reduce the MSW compared with that of FUS or ERY alone, whereas this is not possible for combinations of CPR and AMP, or FUS and AMI (arrows).