Oxidative Stress Survival in a Clinical Saccharomyces cerevisiae Isolate Is Influenced by a Major Quantitative Trait Nucleotide

Abstract

One of the major challenges in characterizing eukaryotic genetic diversity is the mapping of phenotypes that are the cumulative effect of multiple alleles. We have investigated tolerance of oxidative stress in the yeast Saccharomyces cerevisiae, a trait showing phenotypic variation in the population. Initial crosses identified that this is a quantitative trait. Microorganisms experience oxidative stress in many environments, including during infection of higher eukaryotes. Natural variation in oxidative stress tolerance is an important aspect of response to oxidative stress exerted by the human immune system and an important trait in microbial pathogens. A clinical isolate of the usually benign yeast S. cerevisiae was found to survive oxidative stress significantly better than the laboratory strain. We investigated the genetic basis of increased peroxide survival by crossing those strains, phenotyping 1500 segregants, and genotyping of high-survival segregants by hybridization of bulk and single segregant DNA to microarrays. This effort has led to the identification of an allele of the transcription factor Rds2 as contributing to stress response. Rds2 has not previously been associated with the survival of oxidative stress. The identification of its role in the oxidative stress response here is an example of a specific trait that appears to be beneficial to Saccharomyces cerevisiae when growing as a pathogen. Understanding the role of this fungal-specific transcription factor in pathogenicity will be important in deciphering how fungi infect and colonize the human host and could eventually lead to a novel drug target.

Multiple Approaches Detect the Presence of Fungi in Human Breastmilk Samples from Healthy Mothers

“…cerevisiae isolates have been responsible for human infections that are not life threatening except in severely immunocompromised patients where systemic infection may occur 22 . Pathogenic Saccharomyces clinical strains have shown resistance to high oxidative stress conditions 44 . Upon exposing the S .…”

QTL Analysis of High Thermotolerance with Superior and Downgraded Parental Yeast Strains Reveals New Minor QTLs and Converges on Novel Causative Alleles Involved in RNA Processing

“…S. cerevisiae displays many quantitative traits that are also important in other cell types, including industrial microorganisms and cells of higher, multicellular organisms. Such properties include thermotolerance [6] and oxidative stress tolerance [7], the capacity to produce small molecules, such as acetic acid [8] and ethanol tolerance [9], [10]. Other quantitative traits that have been studied in yeast include transcriptional regulation [11], sporulation efficiency [12], telomere length [13], cell morphology traits [14], mitochondrial genome instability [15], global gene expression [16], evolution of biochemical pathways [17] and resistance to chemicals [18].…”

Opportunistic Strains of Saccharomyces cerevisiae: A Potential Risk Sold in Food Products

“…In S. cerevisiae , the main role of proper oxidative stress response virulence has been suggested since a virulent strain mutant in transcription factor Yap1p, the main transcription factor involved in oxidative stress response that is unable to grow under oxidative stress conditions, presented low survival levels in human blood compared with the wild type or the YAP1 reconstituted strain ( Llopis et al, 2012 ). Diezmann and Dietrich (2011) compared hundreds of clinical isolates and showed that they were more resistant to oxidative stress after they verified the central role of oxidative stress resistance in S. cerevisiae virulence.…”