Synthetic inter-species cooperation of host and virus for targeted genetic evolution

Cooperative inter-species interaction is another way of evolution in nature. Such cooperation leading to mutual benefits provides a new view on the interaction of biological systems, and engineering such inter-species interaction offers an opportunity for diverse potential applications in biotechnology. Here we show a synthetic system with artificially created inter-species cooperation of host and virus. A genetically engineered host (Escherichia coli) provides nutrients and energies necessary for virus reproduction, and a genetically engineered virus (phage M13) enhances infected hosts to survive under fatal concentration of antibiotics. We applied the synthetic system to evolve the virus with increasing selective pressure in environment, specifically to evolve a virus-carried heterogeneous gene (luxR), which consequently enhances the ability of infected hosts to survive against antibiotics. As a result we obtained evolved luxR mutants with improved activity by up to 17 folds from a limited number of viruses randomly isolated and generated over a small number of generations. Our synthetic system would provide the significant sight in the principle of system design with regard to the utilization of inter-species cooperation, and also the targeted evolution technique itself. Advancement of the concept of this system would foster more practical and valuable applications.