Fig. 3: Major strain-specific factors govern evolutionary response for simulated strains.

A All else being equal, higher burdens (lower \(\alpha\)), lower private benefits (higher \({\beta }_{\min }\)), and higher inhibition of intracellular Bla (higher \(c\)) are associated with a modest decrease in survivable dose concentrations (dimensionless density reported in yellow to green color) and lower final resistant fractions (resistant fraction reported in blue to red color) at all concentrations. Quantities are dimensionless. B Drivers of the selection dynamics. When antibiotic concentration is high, resistant cells have a growth advantage due to private benefit, which can be suppressed by Bla inhibition. When antibiotic concentration is low, sensitive cells have a growth advantage due to the burden of Bla expression. The length of the two periods is governed by the doses of antibiotic and Bla inhibitor as well as antibiotic degradation. C The simplified criterion \((1 - c)(1 - {\beta }_{m{in}}) \, > \, (1 - \alpha )/\gamma\), where \(\gamma\) represents the maximum lysis coefficient, predicts the outcome of selection dynamics for 10,000 simulated strains with randomized parameters. For each parameter set, we queried each inhibitor concentration and identified the lowest antibiotic concentration for which the cell density was suppressed below 1. We took the lowest resistant fraction in this set as the minimum achievable resistant fraction for doses high enough to suppress the population. The color of each circle reports this value for the corresponding parameter combination. Empty circles indicate that no treatment concentrations achieved sufficient suppression.