title: Comparative genomic analysis reveals a critical role of de novo nucleotide biosynthesis for Saccharomyces cerevisiae virulence.
abstract: In recent years, the number of human infection cases produced by the food related species Saccharomyces cerevisiae has increased. Whereas many strains of this species are considered safe, other 'opportunistic' strains show a high degree of potential virulence attributes and can cause infections in immunocompromised patients. Here we studied the genetic characteristics of selected opportunistic strains isolated from dietary supplements and also from patients by array comparative genomic hybridization. Our results show increased copy numbers of IMD genes in opportunistic strains, which are implicated in the de novo biosynthesis of the purine nucleotides pathway. The importance of this pathway for virulence of S. cerevisiae was confirmed by infections in immunodeficient murine models using a GUA1 mutant, a key gene of this pathway. We show that exogenous guanine, an end product of this pathway in its triphosphorylated form, increases the survival of yeast strains in ex vivo blood infections. Finally, we show the importance of the DNA damage response that activates dNTP biosynthesis in yeast cells during ex vivo blood infections. We conclude that opportunistic yeasts may use an enhanced de novo biosynthesis of the purine nucleotides pathway to increase survival and favor infections in the host.
authors: Instituto de Agroquímica y Tecnología de los Alimentos, CSIC, Valencia, Spain.
authors: Roberto
authors: R
authors: Pérez-Torrado
authors: Instituto de Agroquímica y Tecnología de los Alimentos, CSIC, Valencia, Spain.
authors: Silvia
authors: S
authors: Llopis
authors: Instituto de Agroquímica y Tecnología de los Alimentos, CSIC, Valencia, Spain; Department of Agricultural, Forest and Food Sciences Microbiology and Food Technologies Unit University of Torino, Torino, Italy.
authors: Benedetta
authors: B
authors: Perrone
authors: Instituto de Agroquímica y Tecnología de los Alimentos, CSIC, Valencia, Spain.
authors: Rocío
authors: R
authors: Gómez-Pastor
authors: Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knoell-Institute (HKI), Jena, Germany; Friedrich Schiller University, Jena, Germany.
authors: Bernhard
authors: B
authors: Hube
authors: Instituto de Agroquímica y Tecnología de los Alimentos, CSIC, Valencia, Spain.
authors: Amparo
authors: A
authors: Querol
mesh_terms: D000818:Animals; D001769:Blood / Q000382:microbiology*; D055028:Comparative Genomic Hybridization / Q000379:methods*; D019587:Dietary Supplements / Q000382:microbiology; D004195:Disease Models, Animal; D018628:Gene Dosage; D018816:Genes, cdc; D006801:Humans; D051379:Mice; D009154:Mutation; D011685:Purine Nucleotides / Q000096:biosynthesis*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D014774:Virulence
chemical_list: D011685:Purine Nucleotides; D029701:Saccharomyces cerevisiae Proteins