Telomere length control and transcriptional regulation of subtelomeric adhesins in Candida glabrata
Abstract
The pathogenic yeast Candida glabrata is able to bind in vitro to human epithelial cells. This interaction depends on expression of the adhesin Epa1p. The genome contains a number of EPA1 paralogues which localize to the subtelomeric regions of the C. glabrata. We have identified three hyperadherent mutants of C. glabrata. The first has an insertion adjacent to EPA7, an EPA1-related adhesin. The others disrupt the SIR3 and RIF1 genes of C. glabrata. We show that SIR3 and RIF1 are required for subtelomeric silencing in C. glabrata and that RIF1 regulates telomere length in C. glabrata. We show that the hyperadherent phenotype of the sir3Delta and rif1Delta deletion strains depends primarily on derepression of two novel members of the EPA gene family -EPA6 and EPA7. The sir3Delta and rif1Delta mutants show increased colonization of the kidney in a murine model of disseminated infection and this hypercolonization depends, at least in part, on derepression of EPA6 and EPA7. The analysis here is the first evidence that multiple EPA genes encode adhesins and demonstrates that transcription of at least two of these adhesins is regulated by subtelomeric silencing.
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Other adhesins, cell wall proteins and RNA polymerase II mediator complex subunits including Epa3, Epa7, Epa12, Awp4-6, Pwp1, Pwp3, Med12, Med13 and Med15 have also been implicated in biofilm formation.
“Additionally, other adhesins, cell wall proteins and RNA polymerase II mediator complex subunits including Epa3, Epa7, Epa12, Awp4–6, Pwp1, Pwp3, Med12, Med13 and Med15 have also been implicated in biofilm formation [36,37,40,53,54].”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [36]
The adhesin encoded by EPA6 plays a central role in biofilm formation in C. glabrata.
“Among these, the adhesin encoded by the EPA6 gene, which is regulated by multiple factors including the CgYak1p kinase, subtelomeric silencing, chromatin remodeling Swi/Snf complex components and the transcriptional factor CgCst6, plays a central role [36,37,53].”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [36]
Epa6 and Epa7 are pivotal to adherence under specific environmental conditions.
“Although the in vitro adherence of C. glabrata to epithelial cells is primarily mediated by the Epa1 adhesin [32], Epa6 and Epa7 have been shown to be pivotal to adherence under specific environmental conditions [30,36].”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [36]
The EPA gene family is composed of 17-23 genes depending on the strain.
“The family of EPA genes are composed of 17–23 genes depending on the strain”
From Candida glabrata Biofilms: How Far Have We Come? (2017) · cites this paper as [49]
Candida glabrata clinical isolates are known to have the aldo-keto-reductase superfamily upregulated in the resistant isolates.
“Candida glabrata clinical isolates are known to have the aldo-keto-reductase superfamily upregulated in the resistant isolates.”
From Candida glabrata Biofilms: How Far Have We Come? (2017) · cites this paper as [49]
EPA1, EPA6, and EPA7 are the most important adhesins.
“however, EPA1, EPA6, and EPA7 are the most important adhesins [49].”
From Candida glabrata Biofilms: How Far Have We Come? (2017) · cites this paper as [49]
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- Authors
- Castaño, I., Pan, S., Zupancic, M., Hennequin, C., Dujon, B., & Cormack, B. P.
- Affiliations
- Johns Hopkins University (US)
- Institut Pasteur (FR)
- Corresponding author
- Cormack, Brendan P.
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 2005-01-12
- Volume
- 55
- Issue
- 4
- Pages
- 1246-1258
- ISSN
- 0950-382X (ISSN-L)
- 1365-2958
- OpenAlex
- W1594622192
- Cited by
- 188
- References
- 22
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 9 · 2023: 5 · 2022: 13 · 2021: 6 · 2020: 6 · 2019: 8 · 2018: 12 · 2017: 5 · 2016: 10 · 2015: 11 · 2014: 13 · 2013: 13 · 2012: 10
- FWCI
- 3.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI046223, R01AI46223)
- National Institute of Diabetes and Digestive and Kidney Diseases (2PO1 DK49720, P01DK049720)
- 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, telomere length control, adhesins, Sir3, RIF1, transcriptional regulation, kidney colonization, systemic candidiasis
- MeSH terms
- Animals, Base Sequence, Cell Line, Fungal Proteins, Genotype, Cricetinae, Humans, Kidney, Molecular Sequence Data, Mutation, Plasmids, Transfection, Gene Expression Regulation, Fungal, CHO Cells, Telomere, DNA Primers, Lectins, Candida glabrata
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