Cross-Kingdom Chemical Communication Drives a Heritable, Mutually Beneficial Prion-Based Transformation of Metabolism

In experimental science, organisms are usually studied in isolation, but in the wild, they compete and cooperate in complex communities. We report a system for cross-kingdom communication by which bacteria heritably transform yeast metabolism. An ancient biological circuit blocks yeast from using other carbon sources in the presence of glucose. [GAR+], a protein-based epigenetic element, allows yeast to circumvent this “glucose repression” and use multiple carbon sources in the presence of glucose. Some bacteria secrete a chemical factor that induces [GAR+]. [GAR+] is advantageous to bacteria because yeast cells make less ethanol and is advantageous to yeast because their growth and long-term viability is improved in complex carbon sources. This cross-kingdom communication is broadly conserved, providing a compelling argument for its adaptive value. By heritably transforming growth and survival strategies in response to the selective pressures of life in a biological community, [GAR+] presents a unique example of Lamarckian inheritance. [Display omitted] •Cross-kingdom chemical communication drives heritable changes in yeast metabolism•Metabolic switch confers strong growth advantages to yeast and bacteria alike•Droplet microfluidics enables single-cell study of microbial interactions•This interaction transforms the dynamics of fermentations Through cross-kingdom chemical communication, bacteria can heritably transform yeast metabolism by inducing an epigenetic element, [GAR+], in yeast, which leads to a mutually beneficial outcome for both organisms.