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When the Most Potent Combination of Antibiotics Selects for the Greatest Bacterial Load: The Smile-Frown Transition

Figure 6

Drug checkerboards and isobolograms.

(a) Empirical dose-response checkerboards show population density data on the z-axis versus drug concentration on the x and y-axes. This data was obtained by culturing E. coli sampled from the highly synergistic 50-50 environment at days one and five (the treatment with 4.8 µg/ml ERY and 0.08 µg/ml DOX), it corroborates the known synergism on day 1 and indicates the appearance of a more complex interaction by day 5. Note, 50% inhibition relative to the zero-drug control population is indicated by white blocks; (right) the 70% isobole is highlighted as a green line, indicating an interaction where one drug appears to suppress the other. (b) Isoboles (lines of equal inhibitory effect) are shown based on a numerical filter of the data from (a) (the fitting algorithm and code are described in [50]). Black lines correspond to isoboles in intervals of 10% inhibition, the darkest red areas illustrate increasing drug concentrations with inhibition towards 100%, the darkest blue areas denote inhibition closest to 0%. The white region denotes 50% inhibition.

Figure 6