UME6 , a Novel Filament-specific Regulator of Candida albicans Hyphal Extension and Virulence
Open accessAbstract
The specific ability of the major human fungal pathogen Candida albicans, as well as many other pathogenic fungi, to extend initial short filaments (germ tubes) into elongated hyphal filaments is important for a variety of virulence-related processes. However, the molecular mechanisms that control hyphal extension have remained poorly understood for many years. We report the identification of a novel C. albicans transcriptional regulator, UME6, which is induced in response to multiple host environmental cues and is specifically important for hyphal extension. Although capable of forming germ tubes, the ume6Δ/ume6Δ mutant exhibits a clear defect in hyphal extension both in vitro and during infection in vivo and is attenuated for virulence in a mouse model of systemic candidiasis. We also show that UME6 is an important downstream component of both the RFG1-TUP1 and NRG1-TUP1 filamentous growth regulatory pathways, and we provide evidence to suggest that Nrg1 and Ume6 function together by a negative feedback loop to control the level and duration of filament-specific gene expression in response to inducing conditions. Our results suggest that hyphal extension is controlled by a specific transcriptional regulatory mechanism and is correlated with the maintenance of high-level expression of genes in the C. albicans filamentous growth program.
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Ume6 does not play a major role in virulence in the Galleria mellonella model.
“These results suggest that Ume6, despite its important role in C. auris morphogenesis, does not play a major role in virulence in the Galleria model.”
From Ume6-dependent pathways of morphogenesis and biofilm formation in <i>Candida auris</i> (2024) · cites this paper as [28]
Ume6 is a key regulator of the switch from yeast to hyphal form and of biofilm formation in Candida albicans.
“Because the zinc cluster transcription factor Ume6 is known to be a key regulator of the switch from yeast to hyphal form and of biofilm formation in C. albicans (28–31), we explored its role in C. auris.”
From Ume6-dependent pathways of morphogenesis and biofilm formation in <i>Candida auris</i> (2024) · cites this paper as [28]
Ume6 was shown to play a role in C. albicans virulence.
“Moreover, while Ume6 was shown to play a role in C. albicans virulence (28, 42), we could not reproduce this impact in an insect model of C. auris infection.”
From Ume6-dependent pathways of morphogenesis and biofilm formation in <i>Candida auris</i> (2024) · cites this paper as [28]
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- Authors
- Banerjee, M., Thompson, D. S., Lazzell, A., Carlisle, P. L., Pierce, C., Monteagudo, C., López-Ribot, J. L., & Kadosh, D.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- *Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900;
- The University of Texas at San Antonio (US)
- Universitat de València (ES)
- Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249; and
- Venue
- Molecular Biology of the Cell
- Published
- 2008-04
- Volume
- 19
- Issue
- 4
- Pages
- 1354-1365
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC2291399
- OpenAlex
- W2157151790
- Cited by
- 243
- References
- 3
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 11 · 2023: 16 · 2022: 18 · 2021: 21 · 2020: 15 · 2019: 13 · 2018: 15 · 2017: 15 · 2016: 10 · 2015: 10 · 2014: 18 · 2013: 14 · 2012: 10
- FWCI
- 5.22
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular Biology of the Cell (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Aberdeen University Research Archive (Aberdeen University) (submittedVersion)
- Funders
- University of Texas at San Antonio
- Julius-Maximilians-Universität Würzburg
- National Institutes of Health
- University of California, San Francisco
- University of Texas Health Science Center at San Antonio
- Stanford Bio-X
- National Institute of Allergy and Infectious Diseases (R01AI064562)
- 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
- Ume6, Candida albicans, hyphal extension, germ tube formation, filamentous growth, virulence, systemic candidiasis, transcription factors, negative feedback loop
- MeSH terms
- Animals, Candida albicans, Candidiasis, Disease Models, Animal, DNA, Fungal, Female, Fungal Proteins, Genes, Fungal, Humans, Mice, Inbred BALB C, Models, Biological, Mutation, Repressor Proteins, Transcription Factors, Virulence, Gene Expression Regulation, Fungal, Gene Expression Regulation, Developmental, Oligonucleotide Array Sequence Analysis, Mice
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