Population Density Modulates Drug Inhibition and Gives Rise to Potential Bistability of Treatment Outcomes for Bacterial Infections
A-I: Steady state population growth rate (relative to untreated cells) as a function of cell density for multiple drug concentrations. Drug concentrations are A. Tigecycline concentration = 15 (green), 25 (blue), 50 (red), 100 (black) ng/mL; B. Spectinomycin concentration = 50 (green), 100 (blue), 150 (red), 400 (black) μg/mL; C. Daptomycin concentration = 1.0 (green), 1.25 (blue), 1.50 (red), 3.0 (black) μg/mL; D. Nitrofurantoin concentration = 50 (green), 100 (blue), 125 (red), 250 (black) μg/mL; E. Ciprofloxacin concentration = 100 (green), 150 (blue), 200 (red), 300 (black), 400 (cyan) ng/mL; F. Linezolid concentration = 0.1 (green), 0.5 (blue), 4 (red), 5 (black) μg/mL; G. Ampicillin concentration = 200 (green), 300 (blue), 400 (red), 500 (black) ng/mL; Note that ampicillin growth does not reach steady state on the time-scale of our experiment, so these measurements are effective growth rates averaged over a non-steady state (Figure A in S1 Text). H. Ceftriaxone concentration = 5 (green), 50 (blue), 200 (red), 300 (black) μg/mL; I. Doxycycline concentration = 33 (green), 100 (blue), 333 (red), 500 (black) ng/mL. Statistically significant differences between growth at lowest and highest densities (0.2 and 0.8), intermediate densities (0.4 and 0.6), or both are indicated by *, **, and ***, respectively. Error bars are +/- 1.96 standard error (95% confidence intervals). See also Figures B, C in S1 Text.