A novel role for a glycosylphosphatidylinositol‐anchored aspartyl protease, CgYps1, in the regulation of pH homeostasis in Candida glabrata
Open accessAbstract
Proteases, key virulence factors of many bacterial and fungal pathogens, are pivotally important for nutrient acquisition, invasion and adherence to host cells and evasion/escape from host immune cells. In this study, we report a novel role for CgYps1, member of a family of 11 GPI-linked aspartyl proteases, in a human opportunistic fungal pathogen, Candida glabrata, in the regulation of pH homeostasis under acidic environmental conditions. We show that CgYps1 is required to survive low-external-pH environment and the inability of Cgyps1Δ mutant to maintain pH homeostasis results in intracellular acidification and increased reactive oxygen species (ROS) production. We also provide evidence that the reduced intracellular pH in Cgyps1Δ mutant under acidic conditions is, partly, owing to the diminished activity of a plasma membrane proton pump, CgPma1, an orthologue of a key component of pH homeostasis machinery in Saccharomyces cerevisiae, Pma1. In addition, we have examined C. glabrata's response to low environmental pH via genome-wide expression analysis and several genes required for protein folding/modification and stress response pathways including seven of the CgYPS genes were found to be upregulated. Lastly, we show that C. glabrata responds to acidic environment by reducing total β-glucan levels in the cell wall in a CgYps1-dependent manner.
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CgYPS genes are regulated by various environmental conditions including low pH, thermal stress, macrophage and neutrophil internalization.
“CgYPS genes have been shown to be regulated by various environmental conditions including low pH, thermal stress, macrophage and neutrophil internalization [60,61,62,63].”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [61]
The specific role of CgYPS1 in intracellular pH homeostasis has been attributed, in part, to regulation of the ATPase activity of the plasma membrane proton pump CgPma1.
“This specific role of CgYPS1 in intracellular pH homeostasis has been attributed, in part, to regulation of the ATPase activity of the plasma membrane proton pump, CgPma1 [61].”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [61]
CgYps1 is uniquely required to survive acid stress; CgYPS1 deletion led to low intracellular pH, high ROS levels and cell death under low pH and acidic environmental conditions.
“Of eleven CgYapsins, CgYps1 is uniquely required to survive acid stress, as CgYPS1 deletion led to low intracellular pH, high ROS (reactive oxygen species) levels and cell death under low pH and acidic environmental conditions [61].”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [61]
CgYapsins are pivotal to the regulation of several cellular processes such as maintenance of the cell wall architecture, pH and vacuole homeostasis, biofilm formation and interaction with the host.
“Consistently, CgYapsins are pivotal to the regulation of several cellular processes such as maintenance of the cell wall architecture, pH and vacuole homeostasis, biofilm formation and interaction with the host [58,60,61,64].”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [61]
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- Authors
- Bairwa, G., & Kaur, R.
- Affiliations
- Centre for DNA Fingerprinting and Diagnostics (IN)
- Corresponding author
- Kaur, Rupinder
- ORCID
- Kaur, Rupinder
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 2010-12-23
- Volume
- 79
- Issue
- 4
- Pages
- 900-913
- ISSN
- 0950-382X (ISSN-L)
- 1365-2958
- OpenAlex
- W2163913940
- Cited by
- 47
- References
- 44
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 5 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 4 · 2016: 4 · 2015: 5 · 2014: 3 · 2013: 3 · 2012: 2
- FWCI
- 0.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Council of Scientific and Industrial Research, India
- Centre for DNA Fingerprinting and Diagnostics
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Keywords
- Candida glabrata, pH homeostasis, intracellular acidification, reactive oxygen species, plasma membrane H+-ATPase, genome-wide gene expression, β-glucan, cell wall, opportunistic fungal pathogens
- MeSH terms
- Cell Wall, Cloning, Molecular, Fungal Proteins, Proton-Translocating ATPases, Homeostasis, Hydrogen-Ion Concentration, Mutation, Glycosylphosphatidylinositols, Reactive Oxygen Species, Gene Expression Profiling, Candida glabrata, beta-Glucans, Microbial Viability, Aspartic Acid Proteases
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