Delayed antibiotic exposure induces population collapse in enterococcal communities with drug-resistant subpopulations

The molecular and genetic causes of bacterial antibiotic resistance are increasingly understood, while less is known how these molecular events influence population dynamics. In this work, we show the dynamics of E. faecalis communities exposed to antibiotics can be surprisingly rich, as increasing population size or delaying drug exposure can promote population collapse. We combine experiments in computer-controlled bioreactors with simple mathematical models to reveal density-dependent feedback loops, coupling growth and antibiotic efficacy of populations with drug-resistant (β-lactamase) subpopulations. With a wide range of behavior- population survival, collapse, or one of two qualitatively distinct bistable behaviors where either small or large populations survive- competing density-dependent effects arise: drug-sensitive cell growth increases while drug-resistant cell growth decreases drug efficacy. We experimentally show how populations receiving immediate drug influx may thrive, while identical populations exposed to delayed drug influx (and lower average drug concentrations) collapse. These results illustrate the spread of drug resistant determinants—even in single-species communities—may be governed by counterintuitive dynamics driven by population-level interactions.