A common bacterial metabolite elicits prion-based bypass of glucose repression.

Abstract

Robust preference for fermentative glucose metabolism has motivated domestication of the budding yeast <i>Saccharomyces cerevisiae</i>. This program can be circumvented by a protein-based genetic element, the [<i>GAR</i>⁺] prion, permitting simultaneous metabolism of glucose and other carbon sources. Diverse bacteria can elicit yeast cells to acquire [<i>GAR</i>⁺], although the molecular details of this interaction remain unknown. Here we identify the common bacterial metabolite lactic acid as a strong [<i>GAR</i>⁺] inducer. Transient exposure to lactic acid caused yeast cells to heritably circumvent glucose repression. This trait had the defining genetic properties of [<i>GAR</i>⁺], and did not require utilization of lactic acid as a carbon source. Lactic acid also induced [<i>GAR</i>⁺]-like epigenetic states in fungi that diverged from <i>S. cerevisiae</i> ~200 million years ago, and in which glucose repression evolved independently. To our knowledge, this is the first study to uncover a bacterial metabolite with the capacity to potently induce a prion.