The Role of Community Interactions in Shaping the Evolution of Antibiotic Resistance in Oligo-Mouse- Microbiota

Abstract

Microbial communities are shaped by interspecies interactions that influence bacterial survival, competition, and adaptation, particularly under antibiotic pressure. However, how these interactions impact resistance evolution remains poorly understood. In this study, we investigated the effects of vancomycin exposure on the evolutionary trajectories of Enterococcus faecalis KB1, Bacteroides caecimuris I48, and Clostridium innocuum I46 within the Oligo-Mouse-Microbiota (OMM12) model. Using two experimental evolutions at distinct vancomycin concentrations (0.5 μg/mL and 10 μg/mL), we analyzed species-specific adaptation and the role of interspecies interactions in modulating antibiotic responses. Our findings reveal distinct bacterial responses to vancomycin within monoculture and community settings. E. faecalis KB1 exhibited persistence rather than resistance evolution, maintaining stable minimum inhibitory concentration (MIC) values while surviving prolonged vancomycin exposure. However, its presence in the community remained largely unaffected by interspecies interactions, suggesting its dominance was independent of microbial competition. In contrast, C. innocuum I46, which completely collapsed in monocultures under high vancomycin pressure, managed to persist in the community, indicating that interactions with other bacterial species provided a protective effect. Meanwhile, B. caecimuris I48 not only acquired resistance, as seen in its increased MIC of vancomycin, but also played a regulatory role in modulating E. faecalis KB1’s expansion within the OMM12 microbial community. This study highlights the crucial role of microbial interactions in shaping antibiotic susceptibility and resistance evolution. Resistance is not solely determined by intrinsic bacterial traits but is influenced by competition and metabolic dependencies within the community. Antibiotic selection can restructure microbial communities, leading to shifts in species dominance. Understanding these dynamics is essential for predicting resistance development, optimizing antibiotic treatment strategies, and ensuring the stability of microbial ecosystems.