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Baker's Yeast Clinical Isolates Provide a Model for How Pathogenic Yeasts Adapt to Stress
Vandana Raghavan1, Charles F Aquadro1, Eric Alani1
1Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.
Abstract:
Global outbreaks of drug-resistant fungi such as Candida auris are thought to be due at least in part to excessive use of antifungal drugs. Baker's yeast Saccharomyces cerevisiae has gained importance as an emerging opportunistic fungal pathogen that can cause infections in immunocompromised patients. Analyses of over 1000 S. cerevisiae isolates are providing rich resources to better understand how fungi can grow in human environments. A large percentage of clinical S. cerevisiae isolates are heterozygous across many nucleotide sites, and a significant proportion are of mixed ancestry and/or are aneuploid or polyploid. Such features potentially facilitate adaptation to new environments. These observations provide strong impetus for expanding genomic and molecular studies on clinical and wild isolates to understand the prevalence of genetic diversity and instability-generating mechanisms, and how they are selected for and maintained. Such work can also lead to the identification of new targets for antifungal drugs.
Insights
Drug-resistant fungal infections are rising, partly due to antifungal overuse. Studying baker's yeast (Saccharomyces cerevisiae) reveals genetic diversity that helps fungi adapt to human environments, offering new antifungal drug targets.
Area of Science:
- Mycology
- Genetics
- Infectious Diseases
Background:
- Global rise in drug-resistant fungal pathogens like Candida auris linked to antifungal drug overuse.
- Baker's yeast (Saccharomyces cerevisiae) is an emerging opportunistic pathogen affecting immunocompromised individuals.
- Understanding fungal adaptation to human environments is crucial for combating infections.
Purpose of the Study:
- To analyze genetic diversity in Saccharomyces cerevisiae clinical and wild isolates.
- To investigate mechanisms of genetic instability and adaptation in fungi.
- To identify potential new targets for antifungal drug development.
Main Methods:
- Genomic and molecular analyses of over 1000 Saccharomyces cerevisiae isolates.
- Examination of genetic features such as heterozygosity, mixed ancestry, aneuploidy, and polyploidy.
- Comparative studies of clinical and wild fungal isolates.
Main Results:
- A significant proportion of clinical Saccharomyces cerevisiae isolates exhibit high heterozygosity.
- Many isolates show mixed ancestry, aneuploidy, or polyploidy, indicating genetic instability.
- These genetic features potentially facilitate fungal adaptation to diverse human environments.
Conclusions:
- Genetic diversity and instability in Saccharomyces cerevisiae are key to its adaptation as an opportunistic pathogen.
- Further genomic and molecular studies are essential to understand fungal adaptation mechanisms.
- Identifying these mechanisms can lead to the discovery of novel antifungal drug targets.