Metabolic byproduct utilization and the evolution of mutually beneficial cooperation in <i>Escherichia coli</i>

Understanding how cooperation evolves in microbial populations, particularly under environmental stress such as antibiotic exposure, remains a key topic in evolutionary biology. Here, we investigate cooperative interactions between antibiotic-resistant and antibiotic-sensitive strains of Escherichia coli. Under antibiotic stress, a small number of antibiotic-sensitive strains rapidly evolve into antibiotic-resistant strains. Resistant E. coli produce indole, which induces a protective response in sensitive cells, enabling them to survive in antibiotic stress conditions. In turn, antibiotic-sensitive E. coli could help reduce toxic accumulation of indole, indirectly benefiting the resistant strain. Indole is harmful to the growth of the antibiotic-resistant strain but benefits the antibiotic-sensitive strain by helping turn-on the multi-drug exporter to neutralize the antibiotic. This mutual exchange leads to increased fitness for both strains in cocultures, demonstrating a mechanism by which mutually beneficial cooperation can evolve in bacterial communities. Our findings provide insight into how mutualism can emerge under antibiotic pressure through metabolic byproduct exchange, revealing new dynamics in the evolution of bacterial cooperation.