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 Saccharomyces cerevisiae. This program can be circumvented by a protein-based genetic element, the [GAR+] prion, permitting simultaneous metabolism of glucose and other carbon sources. Diverse bacteria can elicit yeast cells to acquire [GAR+], although the molecular details of this interaction remain unknown. Here we identify the common bacterial metabolite lactic acid as a strong [GAR+] inducer. Transient exposure to lactic acid caused yeast cells to heritably circumvent glucose repression. This trait had the defining genetic properties of [GAR+], and did not require utilization of lactic acid as a carbon source. Lactic acid also induced [GAR+]-like epigenetic states in fungi that diverged from S. cerevisiae ~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.DOI: http://dx.doi.org/10.7554/eLife.17978.001

Reverse Evolution of a Classic Gene Network in Yeast Offers a Competitive Advantage

“…However, we found that the S. cerevisiae isolates associated with the spontaneous fermentation of dairy products have abolished glucose repression when galactose is present. The circumvention of glucose repression is not caused by prions as reported previously [16][17][18], but by sophisticated polygenic evolution centered by the introgression of a whole set of the structural genes in the galactose (GAL) metabolism network from an early diverged lineage. We show here the molecular mechanism underlying the abolishment of glucose repression in the domesticated population of S. cerevisiae and provide new insights into the interactions of the structural genes of the GAL network.…”

Microbial specialization by prions

“…In the presence of glucose, even in small amounts relative to other carbon sources, S. cerevisiae will shut off other catabolic pathways to focus exclusively on utilizing the glucose. This stereotypical programming can be overcome by presence of the [GAR + ] prion, which causes cells to lose glucose repression and become metabolic generalists [11,33,34]. We propose that the ability to alter or inactivate common behaviors using reversible prion switches provides a means to adapt to circumstances in which those behaviors are disadvantageous.…”

A New Transkingdom Dimension to NO Signaling

“…It is estimated that up to 10% of circulating mammalian serum metabolites can be attributed to bacterial origin (Wikoff et al, 2009), and transkingdom communications between bacteria and their eukaryotic associates have long been observed from yeast to man. For example, lactate produced by S. gallinurum robustly induces the heritable expression of the [gar+] prion in Saccharomyces cerevisiae, and so that the yeast overcomes glucose repression (Garcia et al, 2016), short-chain fatty acids (SCFAs), such as acetate and propionate derived from microbial digestion of dietary fibers, can activate signal transduction events downstream of a defined set of orphan G protein-coupled receptors (Tan et al, 2014). However, the molecular mechanisms explaining how these microbial-derived molecules can alter the host's biology remain largely unexplored.…”