Cited by 49Fungal and yeast genetics researchRedox biology and oxidative stressSulfur Compounds in Biology

Glutathione biosynthesis in the yeast pathogens Candida glabrata and Candida albicans: Essential in C. glabrata, and essential for virulence in C. albicans

Yadav, Amit Kumar, Desai, Prashant Ramesh, Rai, Maruti Nandan, Kaur, Rupinder, Ganesan, Kaliannan, Bachhawat, Anand Kumar·2011·Microbiology

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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Crossref · 10.1099/mic.0.045054-0

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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
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

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