The Cell Wall of the Human Pathogen Candida glabrata : Differential Incorporation of Novel Adhesin-Like Wall Proteins
Open accessAbstract
The cell wall of the human pathogen Candida glabrata governs initial host-pathogen interactions that underlie the establishment of fungal infections. With the aim of identifying species-specific features that may directly relate to its virulence, we have investigated the cell wall of C. glabrata using a multidisciplinary approach that combines microscopy imaging, biochemical studies, bioinformatics, and tandem mass spectrometry. Electron microscopy revealed a bilayered wall structure in which the outer layer is packed with mannoproteins. Biochemical studies showed that C. glabrata walls incorporate 50% more protein than Saccharomyces cerevisiae walls and, consistent with this, have a higher mannose/glucose ratio. Evidence is presented that C. glabrata walls contain glycosylphosphatidylinositol (GPI) proteins, covalently bound to the wall 1,6-beta-glucan, as well as proteins linked through a mild-alkali-sensitive linkage to 1,3-beta-glucan. A comprehensive genome-wide in silico inspection showed that in comparison to other fungi, C. glabrata contains an exceptionally large number, 67, of genes encoding adhesin-like GPI proteins. Phylogenetically these adhesin-like proteins form different clusters, one of which is the lectin-like EPA family. Mass spectrometric analysis identified 23 cell wall proteins, including 4 novel adhesin-like proteins, Awp1/2/3/4, and Epa6, which is involved in adherence to human epithelia and biofilm formation. Importantly, the presence of adhesin-like proteins in the wall depended on the growth stage and on the genetic background used, and this was reflected in alterations in adhesion capacity and cell surface hydrophobicity. We propose that the large repertoire of adhesin(-like) genes of C. glabrata contributes to its adaptability and virulence.
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This grouping is less complex than proposed earlier using CBS138 data (seven clusters).
“This grouping is less complex than proposed earlier using CBS138 data (seven clusters) (de Groot et al. 2008).”
From Comparative Genomics of Two Sequential <i>Candida glabrata</i> Clinical Isolates (2017) · cites this paper as de Groot et al. 2008
The majority of Epa adhesins are encoded by sub-telomeric localized genes and regulated by epigenetic SIR-dependent transcriptional silencing.
“The majority of Epa adhesins are encoded by sub-telomeric localized genes and regulated by epigenetic SIR (Silent Information Regulator)-dependent transcriptional silencing [27,29,30,31].”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [27]
The sequenced fecal isolate CBS 138 contains 17 Epa-encoding genes, while the vaginal isolate BG2 contains 23 Epa-encoding genes.
“The sequenced fecal isolate CBS 138 contains 17 Epa-encoding genes, while the widely used vaginal isolate BG2 contains 23 Epa-encoding genes [27,28].”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [27]
The presence of a large number of adhesin genes and their complex environment-dependent differential regulation are likely to help C. glabrata colonize different host niches as well as form biofilms on a wide range of surfaces.
“Therefore, the presence of such a large number of adhesin genes and their complex environment-dependent differential regulation are likely to help C. glabrata colonize different host niches as well as to form biofilms on a wide range of surfaces [27,47,48].”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [27]
The Epa sub-family I contains the PA14 ligand-binding domain, is most well studied, and consists of 17 to 23 proteins depending upon the isolate.
“The Epa (Epithelial Adhesin) sub-family I, containing the PA14 (Anthrax Protective Antigen) ligand-binding domain, is most well studied, and consists of 17 to 23 proteins depending upon the isolate [27,28].”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [27]
C. glabrata possesses a total of 67 putative adhesins, which may mediate adherence to host cells.
“C. glabrata possesses a total of 67 putative adhesins, which may mediate adherence to host cells [27].”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [27]
Groot et al. identified another family of adhesins involved in the first stage of Candida glabrata biofilm development, namely Awp adhesins.
“Groot et al. [52] identified another family of adhesins involved in the first stage of C. glabrata biofilm development, namely Awp adhesins.”
From Candida glabrata Biofilms: How Far Have We Come? (2017) · cites this paper as [52]
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References 78 · Cited by 232
- Authors
- de Groot, P. W. J., Kraneveld, E. A., Yin, Q. Y., Dekker, H. L., Groß, U., Crielaard, W., de Koster, C. G., Bader, O., Klis, F. M., & Weig, M.
- Affiliations
- Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands
- Academic Center for Dentistry Amsterdam (NL)
- University of Amsterdam (NL)
- Universitätsmedizin Göttingen (DE)
- Department of Molecular Biology and Preventive Dentistry, Academic Center for Dentistry Amsterdam, Amsterdam, The Netherlands
- Venue
- Eukaryotic Cell
- Publisher
- American Society for Microbiology
- Published
- 2008-11
- Volume
- 7
- Issue
- 11
- Pages
- 1951-1964
- ISSN
- 1535-9778 (ISSN-L)
- 1535-9786
- PMC
- PMC2583536
- OpenAlex
- W2155403267
- Cited by
- 232
- References
- 78
- Citations by year
- 2026: 12 · 2025: 9 · 2024: 11 · 2023: 11 · 2022: 15 · 2021: 16 · 2020: 17 · 2019: 15 · 2018: 16 · 2017: 19 · 2016: 12 · 2015: 15 · 2014: 10 · 2013: 13 · 2012: 16
- FWCI
- 3.43
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Eukaryotic Cell (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UvA-DARE (University of Amsterdam) (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- VU Research Portal (publishedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- GRO (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Deutsche Forschungsgemeinschaft
- 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, fungal cell wall, mannoproteins, β-1,3-glucan, biofilm formation, cell surface hydrophobicity, virulence, host-pathogen interaction
- MeSH terms
- Amino Acid Sequence, Candidiasis, Cell Wall, Fungal Proteins, Humans, Molecular Sequence Data, Phylogeny, Cell Adhesion Molecules, Sequence Alignment, Genome, Fungal, Saccharomyces cerevisiae Proteins, Candida glabrata
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