Identifying novel genetic determinants for oxidative stress tolerance in Candida glabrata via adaptive laboratory evolution
Publication Date
August 2018
Document Type
Article
Publication Title
Yeast
Volume
35
Issue
11
DOI
10.1002/yea.3352
First Page
605
Last Page
618
Abstract
Candida glabrata (C glabrata) is an important yeast of industrial and medical significance. Resistance to oxidative stress is an important trait affecting its robustness as a production host or virulence as a pathogenic agent, but current understanding of resistance mechanisms is still limited in this fungus. In this study, we rapidly evolved C glabrata population to adapt to oxidative challenge (from 80mM to 350mM of H2O2) through short‐term adaptive laboratory evolution. Adaptive mutants were isolated from evolved populations and subjected to phenotypic and omics analyses to identify potential mechanisms of tolerance to H2O2. Phenotypic characterizations revealed faster detoxification of H2O2 and ability to initiate growth at a higher concentration of the oxidant in the isolated adaptive mutants compared with the wild type. Genome resequencing and genome‐wide transcriptome analysis revealed multiple genetic determinants (eg, CAGL0E01243g, CAGL0F06831g, and CAGL0C00385g) that potentially contribute to enhanced H2O2 resistance. Subsequent experimental verification confirmed that CgCth2 (CAGL0E01243g) and CgMga2 (CAGL0F06831g) are important in C glabrata tolerance to oxidative stress. Transcriptome profiling of adaptive mutants and bioinformatic analysis suggest that NADPH regeneration, modulation of membrane composition, cell wall remodeling, and/or global regulatory changes are involved in C glabrata tolerance to H2O2.
Keywords
adaptive evolution, C glabrata, oxidative stress, stress tolerance
Recommended Citation
Katy Kao. "Identifying novel genetic determinants for oxidative stress tolerance in Candida glabrata via adaptive laboratory evolution" Yeast (2018): 605-618. https://doi.org/10.1002/yea.3352
Comments
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