A synthetic communication system uncovers extracellular immunity that self-limits bacteriophage transmission

Abstract

Intercellular communication enables coordinated action by cells of microbial communities and multicellular organisms, often mediated by molecular exchange of information. Inspired by their success, synthetic biologists have recently started implementing population-level controls in engineered organisms with the aim of expanding circuit size and complexity. Yet, realising the true potential of multicellular synthetic biology requires an expanded communication alphabet as well as quantitative models to predict complex behaviour. Towards that aim, here we repurpose the M13 bacteriophage machinery for cell-to-cell communication between Escherichia coli cells and characterise the signalling dynamics. The fitted quantitative model includes the growth burden of the communication machinery, the relationship between cellular growth phase and the secretion-infection kinetics, and concurrent antibiotic selection. Limitations of deterministic models are demonstrated, with stochastic effects playing a key role in reproducing the observed infection kinetics. Surprisingly, we discover that the M13 minor coat protein pIII is released into the medium to confer extracellular immunity to uninfected cells. In a simulated gut environment, this mechanism enables the phage to farm uninfected bacterial cells for the future, increasing the overall success of both M13 and E. coli. In addition to establishing a tool for intercellular communication, our work uncovers the mutualistic nature of a phage-bacterial relationship that has evolved over long-term coexistence.