Role of glutathione in the oxidative stress response in the fungal pathogen Candida glabrata

Gutiérrez-Escobedo, Guadalupe; Orta-Zavalza, Emmanuel; Castaño, Irene; De Las Peñas, Alejandro

doi:10.1007/s00294-013-0390-1

Cited by 47Fungal and yeast genetics researchRedox biology and oxidative stressSulfur Compounds in Biology

Role of glutathione in the oxidative stress response in the fungal pathogen Candida glabrata

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Gutiérrez-Escobedo, Guadalupe, Orta-Zavalza, Emmanuel, Castaño, Irene, De Las Peñas, Alejandro·2013·Current Genetics

DOI 10.1007/s00294-013-0390-1

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Abstract

Candida glabrata, an opportunistic fungal pathogen, accounts for 18-26 % of all Candida systemic infections in the US. C. glabrata has a robust oxidative stress response (OSR) and in this work we characterized the role of glutathione (GSH), an essential tripeptide-like thiol-containing molecule required to keep the redox homeostasis and in the detoxification of metal ions. GSH is synthesized from glutamate, cysteine, and glycine by the sequential action of Gsh1 (γ-glutamyl-cysteine synthetase) and Gsh2 (glutathione synthetase) enzymes. We first screened for suppressor mutations that would allow growth in the absence of GSH1 (gsh1∆ background) and found a single point mutation in PRO2 (pro2-4), a gene that encodes a γ-glutamyl phosphate reductase and catalyzes the second step in the biosynthesis of proline. We demonstrate that GSH is important in the OSR since the gsh1∆ pro2-4 and gsh2∆ mutant strains are more sensitive to oxidative stress generated by H2O2 and menadione. GSH is also required for Cadmium tolerance. In the absence of Gsh1 and Gsh2, cells show decreased viability in stationary phase. Furthermore, C. glabrata does not contain Saccharomyces cerevisiae high affinity GSH transporter ortholog, ScOpt1/Hgt1, however, our genetic and biochemical experiments show that the gsh1∆ pro2-4 and gsh2∆ mutant strains are able to incorporate GSH from the medium. Finally, GSH and thioredoxin, which is a second redox system in the cell, are not essential for the catalase-independent adaptation response to H2O2.

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The oxidative stress response in C. glabrata is regulated by the sole catalase CgCta1, two superoxide dismutases CgSod1 and CgSod2, and glutathione biosynthetic enzymes CgGsh1 and CgGsh2.
“The environmental stress response in C. glabrata is governed by two transcriptional regulators CgMsn2 and CgMsn4 [38], while the oxidative stress response is regulated by the sole catalase CgCta1 [80], two superoxide dismutases CgSod1 and CgSod2 [81], and glutathione biosynthetic enzymes CgGsh1 and CgGsh2 [82,83].”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [83]

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Authors: Gutiérrez-Escobedo, G., Orta-Zavalza, E., Castaño, I., & De Las Peñas, A.
Affiliations: Institute for Scientific and Technological Research (MX)
ORCID: Castaño, Irene
Venue: Current Genetics
Publisher: Springer Science and Business Media LLC
Published: 2013-03-01
Volume: 59
Issue: 3
Pages: 91-106
ISSN: 0172-8083 (ISSN-L)
1432-0983
DOI: 10.1007/s00294-013-0390-1
OpenAlex: W2006135083
Cited by: 47
References: 72
Citations by year: 2026: 6 · 2025: 1 · 2024: 4 · 2023: 4 · 2022: 4 · 2021: 4 · 2020: 4 · 2019: 4 · 2018: 4 · 2016: 5 · 2015: 4 · 2014: 2 · 2013: 1
FWCI: 1.79
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Current Genetics (publishedVersion)
PubMed (publishedVersion)
Funders: Consejo Nacional de Ciencia y Tecnología (CB-2010-01, 151517)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
Keywords: glutathione, oxidative stress response, Candida glabrata, GSH1, GSH2, glutathione synthesis, proline biosynthesis, PrO2, cadmium tolerance, hydrogen peroxide sensitivity, menadione, thioredoxin, glutathione transporters, redox homeostasis, fungal pathogens
MeSH terms: Glutamate-Cysteine Ligase, Glutathione, Glutathione Synthase, Oxidation-Reduction, Saccharomyces cerevisiae, Thioredoxins, Gene Expression Regulation, Fungal, Point Mutation, Oxidative Stress, Glutamic Acid, Candida glabrata

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Role of glutathione in the oxidative stress response in the fungal pathogen Candida glabrata

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