Figure 1.

Stability of plasmid pNUK73 under different antibiotic regimes. Numerical simulations of the evolutionary model presented in San Millan et al. 2014 with parameter values determined from experimental data and an extinction threshold of ϵ = 0.01. (A) Frequency of plasmid bearing cells under 2 different selection regimes: same antibiotic dose (25% above the MIC of the plasmid-free cells) but with different frequencies of drug exposure (antibiotic use is represented with yellow bars). Note how when the antibiotic is used once weekly the plasmid-bearing population is driven to extinction (red dot), while if the drug is used twice-weekly the plasmid is able to persist indefinitely. (B) Heat map representing the time to extinction of the plasmid-bearing population when exposed to increasing drug concentrations and different periods of drug exposure (from daily exposure, every 2, d etc.). Note that plasmid persistence is observed only at certain combinations of dose and frequency of antibiotic exposure (black region). The positive selection regimes used to obtain the time-series illustrated in (A) are represented with white boxes in the period-dose plane.