When the Most Potent Combination of Antibiotics Selects for the Greatest Bacterial Load: The Smile-Frown Transition
Shown are empirical and modelled bacterial densities (dots and lines, respectively) for 16 different drug proportions, denoted by θ and ranging from 0 (denoting ERY) to 1 (denoting DOX) on the horizontal axis. Population densities, measured as optical densities, are plotted against drug proportion are shown here in a panel of six time points with each blue and red datum 24 hours apart. The data was obtained using E. coli K12 (MC4100) challenged by erythromycin and doxycycline. The smile-frown transition described in the text occurs near 30 h at which point drug synergism is replaced by an antagonism. The model assumes multi-drug efflux is the only resistance mechanism and interpolates the discrete dataset to produce a series of continuous interaction profiles, as shown.