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.
Highlights
The yeast Saccharomyces cerevisiae can be found naturally in many niches in the environment, but it is most commonly known for its role as “baker’s yeast” in either the traditional or industrial fermentative production of bread, beer or wine
This technique allowed us to identify those genes with copy number variations (CNV) in the opportunistic strains compared with non-virulent strains
We focused our study on IMD2, a gene showing increased CNs in the three opportunistic strains compared with laboratory strains (Fig. 2A)
Summary
The yeast Saccharomyces cerevisiae can be found naturally in many niches in the environment, but it is most commonly known for its role as “baker’s yeast” in either the traditional or industrial fermentative production of bread, beer or wine. Several studies have analyzed the potential virulence of this yeast species in vitro [10,11,12,13], while others have used in vivo models [13,14,15,16,17] These reports suggest that some clinical, and non-clinical, S. cerevisiae strains have the potential to cause disease in murine models regardless of the host’s immune status. One of the key genes of this pathway, which encodes an enzyme catalyzing the second pathway step, is GUA1 The importance of this pathway for virulence of S. cerevisiae was confirmed by experimental infections in immunodeficient murine models using a Δgua mutant of the clinical strain D14, isolated from a dietary product. An increased efficiency of dNTP biosynthesis may in turn promote DNA repair after DNA damage produced by neutrophil oxidative bursts
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