Counteraction of antibiotic production and degradation stabilizes microbial communities

A major challenge in theoretical ecology is understanding how natural microbial communities support species diversity(1-8), and in particular how antibiotic producing, sensitive and resistant species coexist(9-15). While cyclic “rock-paper-scissors” interactions can stabilize communities in spatial environments(9-11), coexistence in unstructured environments remains an enigma(12,16). Here, using simulations and analytical models, we show that the opposing actions of antibiotic production and degradation enable coexistence even in well-mixed environments. Coexistence depends on 3-way interactions where an antibiotic degrading species attenuates the inhibitory interactions between two other species. These 3-way interactions enable coexistence that is robust to substantial differences in inherent species growth rates and to invasion by “cheating” species that cease producing or degrading antibiotics. At least two antibiotics are required for stability, with greater numbers of antibiotics enabling more complex communities and diverse dynamical behaviors ranging from stable fixed-points to limit cycles and chaos. Together, these results show how multi-species antibiotic interactions can generate ecological stability in both spatial and mixed microbial communities, suggesting strategies for engineering synthetic ecosystems and highlighting the importance of toxin production and degradation for microbial biodiversity.