Oscillatory dynamics in a bacterial cross protection mutualism
Significance Enzymatic deactivation of antibiotics is a cooperative behavior that can allow resistant cells to protect sensitive cells from antibiotics. The prevalence of this mechanism of antibiotic resistance in clinical isolates and in soil bacteria makes it important both clinically and ecologically. Here, we demonstrate experimentally that two populations of resistant bacteria can form a cross protection mutualism in a two drug environment, allowing the coculture to survive high antibiotic concentrations at which neither of the two strains can survive alone. Moreover, we find that daily growth dilution cycles result in large oscillations in the relative abundances of the two strains, thus demonstrating that mutualisms can display striking dynamical behavior. Cooperation between microbes can enable microbial communities to survive in harsh environments. Enzymatic deactivation of antibiotics, a common mechanism of antibiotic resistance in bacteria, is a cooperative behavior that can allow resistant cells to protect sensitive cells from antibiotics. Understanding how bacterial populations survive antibiotic exposure is important both clinically and ecologically, yet the implications of cooperative antibiotic deactivation on the population and evolutionary dynamics remain poorly understood, particularly in the presence of more than one antibiotic. Here, we show that two Escherichia coli strains can form an effective cross protection mutualism, protecting each other in the presence of two antibiotics (ampicillin and chloramphenicol) so that the coculture can survive in antibiotic concentrations that inhibit growth of either strain alone. Moreover, we find that daily dilutions of the coculture lead to large oscillations in the relative abundance of the two strains, with the ratio of abundances varying by nearly four orders of magnitude over the course of the 3 day period of the oscillation. At modest antibiotic concentrations, the mutualistic behavior enables long term survival of the oscillating populations; however, at higher antibiotic concentrations, the oscillations destabilize the population, eventually leading to collapse. The two strains form a successful cross protection mutualism without a period of coevolution, suggesting that similar mutualisms may arise during antibiotic treatment and in natural environments such as the soil.
Proceedings of the National Academy of Sciences