Emergent antibiotic persistence in a spatially structured synthetic microbial mutualism

Area of Science:

• Microbiology
• Ecology
• Evolutionary Biology

Background:

• Antibiotic persistence (heterotolerance) enables bacterial subpopulations to survive antibiotic treatment, contributing to resistance evolution.
• The role of microbial ecology and community interactions in antibiotic persistence remains largely unexplored.

Purpose of the Study:

• To investigate how microbial ecology, specifically cross-feeding and spatial structure in a synthetic community, influences antibiotic persistence.
• To determine the emergent effects of interspecies interactions on bacterial survival under antibiotic stress.

Main Methods:

• Utilized a synthetic two-species mutualism of Escherichia coli and Salmonella enterica.
• Tracked ampicillin-induced bacterial death on agar surfaces using time-series fluorescent microscopy.
• Quantified antibiotic persister formation in monocultures versus cocultures.

Main Results:

• Escherichia coli formed up to 55 times more antibiotic persisters in a cross-feeding coculture with Salmonella enterica compared to monoculture.
• High persistence was an emergent phenomenon not solely explained by species presence, cross-feeding, nutrient levels, or mutations.
• Increased cell-to-cell variation in lag time was observed in E. coli within the mutualistic coculture.

Conclusions:

• The combination of cross-feeding and spatial structure in microbial communities can emergently drive high antibiotic persistence.
• Spatially structured interactions and ecological factors are crucial for understanding bacterial resilience and antibiotic treatment outcomes.