Expression levels of a filament-specific transcriptional regulator are sufficient to determine Candida albicans morphology and virulence
Open accessAbstract
Candida albicans , the major human fungal pathogen, undergoes a reversible morphological transition from single yeast cells to pseudohyphal and hyphal filaments (elongated cells attached end-to-end). Because typical C. albicans infections contain a mixture of these morphologies it has, for many years, been difficult to assess the relative contribution of each form to virulence. In addition, the regulatory mechanisms that determine growth in pseudohyphal and hyphal morphologies are largely unknown. To address these questions we have generated a C. albicans strain that can be genetically manipulated to grow completely in the hyphal form under non-filament-inducing conditions in vitro. This was achieved by inducing high-level constitutive expression of UME6 , a recently identified filament-specific transcriptional regulator of C. albicans hyphal extension. We show that high-level UME6 expression significantly increases hyphal formation and promotes virulence in a mouse model of systemic candidiasis. Our results strongly suggest that shifting the morphology of a C. albicans population toward the hyphal form, and/or increasing hyphal-specific gene expression, during the course of infection is sufficient to improve virulence potential. We also demonstrate that lower levels of UME6 expression specify growth largely in the pseudohyphal form and that increasing UME6 levels is sufficient to cause cells to gradually shift from pseudohyphal to hyphal morphology. In addition, we show that UME6 levels differentially induce the expression of several known filament-specific transcripts. These findings suggest that a common transcriptional regulatory mechanism functions to specify both pseudohyphal and hyphal morphologies in a dosage-dependent manner.
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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 [42]
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 [42]
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Ume6-dependent pathways of morphogenesis and biofilm formation in <i>Candida auris</i>
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- Authors
- Carlisle, P. L., Banerjee, M., Lazzell, A., Monteagudo, C., López-Ribot, J. L., & Kadosh, D.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- The University of Texas at San Antonio (US)
- Universitat de València (ES)
- Department of Biology, University of Texas, One UTSA Circle, San Antonio, TX 78249; and
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-01-13
- Volume
- 106
- Issue
- 2
- Pages
- 599-604
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2626749
- OpenAlex
- W1969395447
- Cited by
- 215
- References
- 2
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 6 · 2023: 13 · 2022: 13 · 2021: 6 · 2020: 9 · 2019: 18 · 2018: 13 · 2017: 14 · 2016: 10 · 2015: 8 · 2014: 11 · 2013: 13 · 2012: 13
- FWCI
- 6.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI064562)
- National Institute of Dental and Craniofacial Research (DE14318, T32DE014318)
- 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 albicans, Ume6, hyphal morphogenesis, yeast-to-hypha transition, fungal virulence, systemic candidiasis, transcriptional regulation
- MeSH terms
- Animals, Candida albicans, Candidiasis, Disease Models, Animal, Transcription Factors, Transcription, Genetic, Virulence, Hyphae, Mice
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