<b>Phenotypic plasticity of antibiotic resistance, metabolism byproduct utilization and the evolution of mutually beneficial cooperation in </b><b><i>Escherichia coli</i></b>

In the absence of tag-based donation and recognition, explaining how cooperative individuals become positively assorted in populations often presents a challenge. Additional non-tag based mechanisms are required to explain why some individuals pay the costs of providing others benefits that may not be initially reciprocated, and how cooperative individuals will meet other similar individuals when mutation rates are low. Here, we show that some <i>Escherichia coli </i>cells under increasing antibiotic exposure plastically evolve into antibiotic resistant individuals able to protect antibiotic sensitive individuals from antibiotic exposure. The resulting antibiotic resistant strain then reversibly evolved to be antibiotic sensitive in an antibiotic-free medium. An additional experiment showed that antibiotic-sensitive <i>E. coli</i> could help reduce the concentration of indole produced by the antibiotic-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. The utilization of indole by antibiotic-resistant cells benefits antibiotic-sensitive cells and also helps nullify the effects of indole on the antibiotic resistant strain thus enabling mutually beneficial cooperation to evolve.