title: A common bacterial metabolite elicits prion-based bypass of glucose repression.
abstract: Robust preference for fermentative glucose metabolism has motivated domestication of the budding yeastSaccharomyces 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 fromS. 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.
authors.affiliation: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, United States.
authors.forename: David M
authors.identifier: 0000-0003-0600-9527
authors.initials: DM
authors.lastname: Garcia
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States.
authors.forename: David
authors.identifier: 0000-0002-6477-4078
authors.initials: D
authors.lastname: Dietrich
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States.
authors.forename: Jon
authors.identifier: 0000-0003-0213-8356
authors.initials: J
authors.lastname: Clardy
authors.affiliation: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, United States.|Department of Developmental Biology, Stanford University School of Medicine, Stanford, United States.
authors.forename: Daniel F
authors.identifier: 0000-0003-3497-5888
authors.initials: DF
authors.lastname: Jarosz
mesh_terms: D057465:Catabolite Repression; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism*; D053858:Metabolic Networks and Pathways / Q000235:genetics; D011328:Prions / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*
chemical_list: D011328:Prions; D019344:Lactic Acid; D005947:Glucose
keywords: Dekkera bruxellensis; S. cerevisiae; Staphylococcus gallinarum; catabolite repression; chromosomes; genes; infectious disease; lactic acid; microbiology; molecular communication; prion