Cooperative antibiotic response in coupled biofilm and planktonic E. faecalis communities

The response of bacterial communities to antibiotic treatment is shaped by complex social interactions. A clinically relevant example is the inactivation of beta-lactam antibiotics by intracellular beta-lactamase in E. faecalis resistant strains. Resistant bacteria act as antibiotic sinks, detoxifying the environment and allowing sensitive bacteria to survive treatment through a long-range cooperative interaction. In this work, we study strongly coupled planktonic and biofilm populations of mixed sensitive-resistant E. faecalis bacteria under antibiotic stress using fluorescent microscopy. The presence of resistant bacteria in the system is capable of restoring both planktonic and biofilm populations at super-inhibitory drug concentrations. We show that a beta-lactam antibiotic with or without the addition of a beta-lactam inhibitor can lead to the spread of resistance by a population inversion effect, characterized by a non-monotonic relation between initial and final fractions of resistant bacteria. The effect is observed in both the planktonic and biofilm populations and is regulated by the total initial cell density. A well-mixed model with competition mediated by resource sharing and cooperation from global degradation of toxins predicts the experimentally observed behavior.