Spatial population dynamics of bacterial colonies with social antibiotic resistance

Abstract

Bacteria frequently inhabit surface-attached communities where rich "social" interactions can significantly alter their population-level behavior, including their response to antibiotics. Understanding these collective effects in spatially heterogeneous communities is an ongoing challenge. Here, we investigated the spatial organization that emerges from antibiotic exposure in initially randomly distributed communities containing antibiotic-resistant and -sensitive strains of E. faecalis, an opportunistic pathogen. We identified that a range of complex spatial structures emerged in the population homeland--the inoculated region that microbes inhabit prior to range expansion--, which depended on initial colony composition and antibiotic concentration. We found that these arrangements were explained by cooperative interactions between resistant and sensitive subpopulations with a variable spatial scale, the result of dynamic zones of protection afforded to sensitive cells by growing populations of enzyme-producing resistant neighbors. Using a combination of experiments and mathematical models, we explored the complex spatiotemporal interaction dynamics that create these patterns, and predicted spatial arrangements of sensitive and resistant subpopulations under new conditions. We illustrated how spatial population dynamics in the homeland affect subsequent range expansion, both because they modulate the composition of the initial expanding front, and through long-range cooperation between the homeland and the expanding region. Finally, we showed that these spatial constraints resulted in populations whose size and composition differed markedly from matched populations in well-stirred (planktonic) cultures. These findings underscore the importance of spatial structure and cooperation, long-studied features in theoretical ecology, for determining the fate of bacterial communities under antibiotic exposure. SignificanceInteractions between bacteria are common, particularly in the crowded surface-associated communities that occur anywhere from natural ecosystems to the human body to medical devices. Antibiotic resistance can be influenced by these "social" interactions, making it difficult to predict how spatial communities respond to antibiotic. Here, we show that complex spatial arrangements emerge when initially randomly distributed populations of antibiotic-resistant and -sensitive E. faecalis, a microbial pathogen, are exposed to antibiotic. Using mathematical models and experiments, we show how local competition and dynamic-range cross-protection drive pattern formation. As a result, these spatially structured populations respond differently to antibiotics than well-mixed communities. Our findings elucidate how "social" antibiotic resistance affects spatially structured bacterial communities, a step towards predicting and controlling resistance.