Glutathione biosynthesis in the yeast pathogens Candida glabrata and Candida albicans: Essential in C. glabrata, and essential for virulence in C. albicans
Abstract
Redox pathways play a key role in pathogenesis. Glutathione, a central molecule in redox homeostasis in yeasts, is an essential metabolite, but its requirements can be met either from endogenous biosynthesis or from the extracellular milieu. In this report we have examined the importance of glutathione biosynthesis in two major human opportunistic fungal pathogens, Candida albicans and Candida glabrata. As the genome sequence of C. glabrata had suggested the absence of glutathione transporters, we initially investigated exogenous glutathione utilization in C. glabrata by disruption of the MET15 gene, involved in methionine biosynthesis. We observed an organic sulphur auxotrophy in a C. glabrata met15Δ strain; however, unlike its Saccharomyces cerevisiae counterpart, the C. glabrata met15Δ strain was unable to grow on exogenous glutathione. This inability to grow on exogenous glutathione was demonstrated to be due to the lack of a functional glutathione transporter, despite the presence of a functional glutathione degradation machinery (the Dug pathway). In the absence of the ability to obtain glutathione from the extracellular medium, we examined and could demonstrate that γ-glutamyl cysteine synthase, the first enzyme of glutathione biosynthesis, was essential in C. glabrata. Further, although γ-glutamyl cysteine synthase has been reported to be non-essential in C. albicans, we report here for what is believed to be the first time that the enzyme is required for survival in human macrophages in vitro, as well as for virulence in a murine model of disseminated candidiasis. The essentiality of γ-glutamyl cysteine synthase in C. glabrata, and its essentiality for virulence in C. albicans, make the enzyme a strong candidate for antifungal development.
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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 [82]
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- Authors
- Yadav, A. K., Desai, P. R., Rai, M. N., Kaur, R., Ganesan, K., & Bachhawat, A. K.
- Affiliations
- Institute of Microbial Technology (IN)
- Centre for DNA Fingerprinting and Diagnostics (IN)
- Venue
- Microbiology
- Publisher
- Microbiology Society
- Published
- 2011-02-01
- Volume
- 157
- Issue
- 2
- Pages
- 484-495
- ISSN
- 1350-0872 (ISSN-L)
- 1465-2080
- OpenAlex
- W2143620551
- Cited by
- 49
- References
- 37
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 1 · 2019: 5 · 2018: 5 · 2017: 4 · 2016: 4 · 2015: 4 · 2014: 2 · 2013: 4 · 2012: 1
- FWCI
- 0.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Council of Scientific and Industrial Research, India
- 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 synthesis, Candida glabrata, Candida albicans, glutathione transporters, redox homeostasis, virulence, systemic candidiasis, macrophage survival, methionine biosynthesis, antifungal drug targets, opportunistic fungal pathogens
- MeSH terms
- Animals, Candida albicans, Cell Line, Cloning, Molecular, Fungal Proteins, Glutamate-Cysteine Ligase, Glutathione, Humans, Male, Mice, Inbred BALB C, Mutation, Oxidation-Reduction, Virulence, Genes, Essential, Candida glabrata, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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