Identification and Characterization of TUP1-Regulated Genes in Candida albicans

Braun, Burkhard R; Head, W Steven; Wang, Ming X; Johnson, Alexander D

doi:10.1093/genetics/156.1.31

Cited by 306Fungal and yeast genetics researchAntifungal resistance and susceptibilityFungal Infections and Studies

Identification and Characterization of TUP1-Regulated Genes in Candida albicans

Braun, Burkhard R, Head, W Steven, Wang, Ming X, Johnson, Alexander D·2000·Genetics

DOI 10.1093/genetics/156.1.31

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Abstract

TUP1 encodes a transcriptional repressor that negatively controls filamentous growth in Candida albicans. Using subtractive hybridization, we identified six genes, termed repressed by TUP1 (RBT), whose expression is regulated by TUP1. One of the genes (HWP1) has previously been characterized, and a seventh TUP1-repressed gene (WAP1) was recovered due to its high similarity to RBT5. These genes all encode secreted or cell surface proteins, and four out of the seven (HWP1, RBT1, RBT5, and WAP1) encode putatively GPI-modified cell wall proteins. The remaining three, RBT2, RBT4, and RBT7, encode, respectively, an apparent ferric reductase, a plant pathogenesis-related protein (PR-1), and a putative secreted RNase T2. The expression of RBT1, RBT4, RBT5, HWP1, and WAP1 was induced in wild-type cells during the switch from the yeast form to filamentous growth, indicating the importance of TUP1 in regulating this process and implicating the RBTs in hyphal-specific functions. We produced knockout strains in C. albicans for RBT1, RBT2, RBT4, RBT5, and WAP1 and detected no phenotypes on several laboratory media. However, two animal models for C. albicans infection, a rabbit cornea model and a mouse systemic infection model, revealed that rbt1Δ and rbt4Δ strains had significantly reduced virulence. TUP1 appears, therefore, to regulate many genes in C. albicans, a significant fraction of which are induced during filamentous growth, and some of which participate in pathogenesis.

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In C. albicans, filamentation caused by perturbations in Hsp90 is associated with upregulation of filament-associated genes such as HWP1, ECE1, and RBT1.
“In C. albicans, filamentation caused by perturbations in Hsp90 was associated with upregulation of filament-associated genes such as HWP1, ECE1, and RBT1, consistent with previous reports (21, 41).”
From Genetic Analysis of Candida auris Implicates Hsp90 in Morphogenesis and Azole Tolerance and Cdr1 in Azole Resistance (2019) · cites this paper as [41]

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Self-citation

Authors: Braun, B. R., Head, W. S., Wang, M. X., & Johnson, A. D.
Affiliations: University of California, San Francisco (US)
Vanderbilt University (US)
Corresponding author: Braun, Burkhard R
ORCID: Johnson, Alexander D
Venue: Genetics
Publisher: Oxford University Press (OUP)
Published: 2000-09-01
Volume: 156
Issue: 1
Pages: 31-44
ISSN: 0016-6731 (ISSN-L)
1943-2631
DOI: 10.1093/genetics/156.1.31
OpenAlex: W1893303563
Cited by: 306
References: 53
Citations by year: 2026: 4 · 2025: 8 · 2024: 4 · 2023: 10 · 2022: 8 · 2021: 10 · 2020: 10 · 2019: 8 · 2018: 11 · 2017: 12 · 2016: 9 · 2015: 10 · 2014: 11 · 2013: 21 · 2012: 9
FWCI: 5.31
Type: journal article
Language: en
Open access: closed
Licence: academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations: Genetics (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01ey001621-22)
National Eye Institute (EY 01621)
National Institute of General Medical Sciences (GM37049, R01GM037049)
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: Tup1, Candida albicans, transcriptional repression, filamentous growth, HWP1, secreted proteins, ferric reductase, RNase T2, virulence, yeast-to-hypha transition, knockout strains
MeSH terms: Amino Acid Sequence, Animals, Candida albicans, Candidiasis, Corneal Diseases, Fungal Proteins, Genes, Fungal, Mice, Inbred BALB C, Molecular Sequence Data, Nuclear Proteins, Phenotype, Rabbits, Repressor Proteins, Virulence, Gene Expression Regulation, Fungal, Conserved Sequence, Gene Deletion, Sequence Homology, Amino Acid, Saccharomyces cerevisiae Proteins, Mice

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Identification and Characterization of TUP1-Regulated Genes in Candida albicans

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