Phenotypic plasticity of antibiotic resistance, metabolism byproduct utilization and the evolution of mutually beneficial cooperation in Escherichia coli

Although tag-based donation and recognition have well explained how the cooperative individuals are positively assorted if the cooperative individuals possess some signals and are also able to detect such signals, an additional mechanism is required to explain why some individuals pay the costs of evolving such a tag that may not be rewarded subsequently, and how such tag-based cooperative individuals will meet other similar individuals with a very low mutation rate. Here, we show that many and even all Escherichia coli bacteria cells in the increased antibiotic concentration will plastically evolve to be antibiotic resistant individuals who could protect antibiotic sensitive strain from the attack of antibiotics, and the antibiotic resistant strain could reversibly evolve to be antibiotic sensitive in non-antibiotic supplement medium but in a harsher environment with low glucose. A further experiment showed that antibiotic-sensitive E. coli strain could in turn help reduce the concentration of indole produced by the resistant strain. This metabolic product 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 discharge the antibiotic. The utilization of metabolism byproduct indole produced by antibiotic-resistant cells benefits antibiotic-sensitive cells, while the indole-absorbing service of antibiotic sensitive cells unconsciously help in nullifying the indole side effect on antibiotic resistant strain, and a mutual benefit cooperation could therefore evolve. ### Competing Interest Statement The authors have declared no competing interest.