Spatial pattern formation of bacterial colonies with social antibiotic resistance

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 patterns emerge 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 patterns were explained by cooperative interactions 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 patterns under new conditions. We illustrated how pattern formation in the homeland affects subsequent range expansion, both because it modulates 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 antibiotic-resistant communities.