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Cited by 4Fungal and yeast genetics researchAntifungal resistance and susceptibilityYeasts and Rust Fungi Studies

The Epithelial adhesin 1 tandem repeat region mediates protein display through multiple mechanisms

Open access
Raposo, Colin J, McElroy, Kyle A, Fuchs, Stephen M·2020·FEMS Yeast Research
DOI 10.1093/femsyr/foaa018PMC PMC7199969

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Abstract

The pathogenic yeast Candida glabrata is reliant on a suite of cell surface adhesins that play a variety of roles necessary for transmission, establishment and proliferation during infection. One particular adhesin, Epithelial Adhesin 1 [Epa1p], is responsible for binding to host tissue, a process which is essential for fungal propagation. Epa1p structure consists of three domains: an N-terminal intercellular binding domain responsible for epithelial cell binding, a C-terminal GPI anchor for cell wall linkage and a serine/threonine-rich linker domain connecting these terminal domains. The linker domain contains a 40-amino acid tandem repeat region, which we have found to be variable in repeat copy number between isolates from clinical sources. We hypothesized that natural variation in Epa1p repeat copy may modulate protein function. To test this, we recombinantly expressed Epa1p with various repeat copy numbers in S. cerevisiae to determine how differences in repeat copy number affect Epa1p expression, surface display and binding to human epithelial cells. Our data suggest that repeat copy number variation has pleiotropic effects, influencing gene expression, protein surface display and shedding from the cell surface of the Epa1p adhesin. This study serves to demonstrate repeat copy number variation can modulate protein function through a number of mechanisms in order to contribute to pathogenicity of C. glabrata.

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  • Previous studies show that variations in tandem repeat copy numbers within fungal adhesin proteins can affect their surface hydrophobicity, cell surface display, and protein shedding, ultimately influencing their functions.

    “This agrees with previous studies showing that variations in tandem repeat copy numbers within fungal adhesin proteins can affect their surface hydrophobicity, cell surface display, and protein shedding, ultimately influencing their functions52,53.”

    From Adhesin Als4112 promotes Candida auris skin colonization through interactions with keratinocytes and extracellular matrix proteins (2025) · cites this paper as [52]

    The Abstract reports that Epa1p tandem-repeat copy number affects surface display, shedding, and protein function; the Results section on shedding reports less shedding as copy number increases. Our copy does not link repeat copy number to cell-surface hydrophobicity. Its Introduction mentions a hydrophobic signal peptide, which is a different property. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Raposo, C. J., McElroy, K. A., & Fuchs, S. M.
Affiliations
Tufts University (US)
Corresponding author
Fuchs, Stephen M
ORCID
Venue
FEMS Yeast Research
Publisher
Oxford University Press (OUP)
Published
2020-04-17
Volume
20
Issue
3
ISSN
  • 1567-1356 (ISSN-L)
  • 1567-1364
DOI
10.1093/femsyr/foaa018
PMC
PMC7199969
OpenAlex
W3017366181
Cited by
4
References
3
Citations by year
2025: 2 · 2023: 1 · 2021: 1
FWCI
0.16
Type
journal article
Language
en
Open access
Licence
Locations
  • FEMS Yeast Research (publishedVersion, cc-by-nc)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • Army Research Office (W911NF-16–1-0175, W911NF-19-0299)
  • American Society for Biochemistry and Molecular Biology
  • Tufts University Summer Scholars
  • Justin and Ashleigh Nelson
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Yeasts and Rust Fungi Studies
Keywords
Candida glabrata, cell surface adhesins, glycosylphosphatidylinositol anchor, gene expression regulation, fungal pathogenicity, clinical isolates
MeSH terms
Candidiasis, Cell Adhesion, Epithelial Cells, Fungal Proteins, HeLa Cells, Humans, Protein Binding, Saccharomyces cerevisiae, Gene Expression, Tandem Repeat Sequences, Candida glabrata, DNA Copy Number Variations

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