The High-Osmolarity Glycerol Response Pathway in the Human Fungal Pathogen Candida glabrata Strain ATCC 2001 Lacks a Signaling Branch That Operates in Baker's Yeast
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The high-osmolarity glycerol (HOG) mitogen-activated protein (MAP) kinase pathway mediates adaptation to high-osmolarity stress in the yeast Saccharomyces cerevisiae . Here we investigate the function of HOG in the human opportunistic fungal pathogen Candida glabrata. C. glabrata sho1 Δ (Cg sho1 Δ) deletion strains from the sequenced ATCC 2001 strain display severe growth defects under hyperosmotic conditions, a phenotype not observed for yeast sho1 Δ mutants. However, deletion of Cg SHO1 in other genetic backgrounds fails to cause osmostress hypersensitivity, whereas cells lacking the downstream MAP kinase Pbs2 remain osmosensitive. Notably, ATCC 2001 Cg sho1 Δ cells also display methylglyoxal hypersensitivity, implying the inactivity of the Sln1 branch in ATCC 2001. Genomic sequencing of Cg SSK2 in different C. glabrata backgrounds demonstrates that ATCC 2001 harbors a truncated and mutated Cg ssk2 - 1 allele, the only orthologue of yeast SSK2/SSK22 genes. Thus, the osmophenotype of ATCC 2001 is caused by a point mutation in Cg ssk2 - 1 , which debilitates the second HOG pathway branch. Functional complementation experiments unequivocally demonstrate that HOG signaling in yeast and C. glabrata share similar functions in osmostress adaptation. In contrast to yeast, however, Cg sho1 Δ mutants display hypersensitivity to weak organic acids such as sorbate and benzoate. Hence, CgSho1 is also implicated in modulating weak acid tolerance, suggesting that HOG signaling in C. glabrata mediates the response to multiple stress conditions.
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The CBS138 strain of C. glabrata naturally carries a mutation that inactivates the SSK2 component of the HOG signaling pathway.
“The CBS138 strain of C. glabrata naturally carries a mutation that inactivates the SSK2 component of the HOG signaling pathway (41).”
From Echinocandin tolerance and persistence <i>in vitro</i> are regulated by calcineurin signaling in <i>Candida glabrata</i> (2026) · cites this paper as [41]
The Results (p. 6) state that ATCC 2001 carries a truncated, nonfunctional SSK2 allele, and the Discussion (p. 8) attributes its inactive HOG signaling branch to an SSK2 point mutation. Our copy does not identify ATCC 2001 as CBS138, so it does not establish the claim for the strain named in the citing sentence. (LLM, conf=0.83)
Experimental — accuracy not yet measuredSSK2 encodes a MAPKKK that phosphorylates and activates Pbs2, a MAPKK, that in turn phosphorylates Hog1, a MAPK that responds to high-osmolarity signals.
“SSK2 encodes a MAPKKK that phosphorylates and activates Pbs2, a MAPKK, that in turn phosphorylates Hog1, a MAPK that responds to high-osmolarity signals (41).”
From Echinocandin tolerance and persistence <i>in vitro</i> are regulated by calcineurin signaling in <i>Candida glabrata</i> (2026) · cites this paper as [41]
The HOG signaling pathway is naturally polymorphic in different strains of C. glabrata, contributing to variation in resistance to micafungin and other stressors, as well as variation in tolerance and persistence within the species.
“Interestingly, the HOG signaling pathway is naturally polymorphic in different strains of C. glabrata, contributing to variation in the resistance to micafungin (21) and other stressors (41), as well as variation in tolerance and persistence within the species.”
From Echinocandin tolerance and persistence <i>in vitro</i> are regulated by calcineurin signaling in <i>Candida glabrata</i> (2026) · cites this paper as [41]
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- Authors
- Gregori, C., Schüller, C., Roetzer, A., Schwarzmüller, T., Ammerer, G., & Kuchler, K.
- Affiliations
- Max Perutz Labs (AT)
- Department of Biochemistry and Molecular Cell Biology, Max F. Perutz Laboratories, University of Vienna, A-1030 Vienna, Austria
- University of Vienna (AT)
- Department of Medical Biochemistry, Max F. Perutz Laboratories, Medical University Vienna
- Venue
- Eukaryotic Cell
- Publisher
- American Society for Microbiology
- Published
- 2007-09
- Volume
- 6
- Issue
- 9
- Pages
- 1635-1645
- ISSN
- 1535-9778 (ISSN-L)
- 1535-9786
- PMC
- PMC2043364
- OpenAlex
- W2140194903
- Cited by
- 57
- References
- 49
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 7 · 2015: 4 · 2014: 2 · 2013: 4 · 2012: 4
- FWCI
- 1.86
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Eukaryotic Cell (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Phaidra (Universität Wien) (submittedVersion, cc-by-nc-nd)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Yeasts and Rust Fungi Studies
- Keywords
- Candida glabrata, high-osmolarity glycerol pathway, Sho1, Sln1, sorbates, benzoate, hyperosmotic stress, Saccharomyces cerevisiae comparison
- MeSH terms
- Acids, Amino Acid Sequence, Fungal Proteins, Glycerol, Hot Temperature, Humans, Membrane Proteins, Molecular Sequence Data, Osmolar Concentration, Saccharomyces cerevisiae, Signal Transduction, Genome, Fungal, Gene Deletion, Point Mutation, MAP Kinase Kinase Kinases, Candida glabrata
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