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

The molecular underpinnings of antibiotic resistance are increasingly understood, but less is known about how these molecular events influence microbial dynamics on the population scale. Here, we show that the dynamics of E. faecalis communities exposed to antibiotics can be surprisingly rich, revealing scenarios where increasing population size or delaying drug exposure can promote population collapse. Specifically, we demonstrate how density-dependent feedback loops couple population growth and antibiotic efficacy when communities include drug-resistant subpopulations, leading to a wide range of behavior, including population survival, collapse, or one of two qualitatively distinct bistable behaviors where survival is favored in either small or large populations. These dynamics reflect competing density-dependent effects of different subpopulations, with growth of drug-sensitive cells increasing but growth of drug-resistant cells decreasing effective drug inhibition. Finally, we demonstrate how populations receiving immediate drug influx may sometimes thrive, while identical populations exposed to delayed drug influx collapse.