Role of Bcr1-Activated Genes Hwp1 and Hyr1 in Candida Albicans Oral Mucosal Biofilms and Neutrophil Evasion
Open accessAbstract
Candida albicans triggers recurrent infections of the oropharyngeal mucosa that result from biofilm growth. Prior studies have indicated that the transcription factor Bcr1 regulates biofilm formation in a catheter model, both in vitro and in vivo. We thus hypothesized that Bcr1 plays similar roles in the formation of oral mucosal biofilms and tested this hypothesis in a mouse model of oral infection. We found that a bcr1/bcr1 mutant did not form significant biofilm on the tongues of immunocompromised mice, in contrast to reference and reconstituted strains that formed pseudomembranes covering most of the tongue dorsal surface. Overexpression of HWP1, which specifies an epithelial adhesin that is under the transcriptional control of Bcr1, partly but significantly rescued the bcr1/bcr1 biofilm phenotype in vivo. Since HWP1 overexpression only partly reversed the biofilm phenotype, we investigated whether additional mechanisms, besides adhesin down-regulation, were responsible for the reduced virulence of this mutant. We discovered that the bcr1/bcr1 mutant was more susceptible to damage by human leukocytes when grown on plastic or on the surface of a human oral mucosa tissue analogue. Overexpression of HYR1, but not HWP1, significantly rescued this phenotype. Furthermore a hyr1/hyr1 mutant had significantly attenuated virulence in the mouse oral biofilm model of infection. These discoveries show that Bcr1 is critical for mucosal biofilm infection via regulation of epithelial cell adhesin and neutrophil function.
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Hyr1 is a hyphal-specific protein that inhibits C. albicans killing by neutrophils and contributes to virulence in mouse models of disseminated candidiasis and OPC.
“This hyphal-specific protein has previously been found to inhibit C. albicans killing by neutrophils and contribute to virulence in mouse models of both disseminated candidiasis and OPC, but its host cell receptor was unknown [24,25].”
From Candida albicans stimulates formation of a multi-receptor complex that mediates epithelial cell invasion during oropharyngeal infection (2023) · cites this paper as [25]
The Results and Discussion (page not supplied) describe Hyr1 as expressed during hyphal development and report resistance to neutrophil killing and reduced fungal burden for the hyr1/hyr1 mutant in a mouse oral infection model. Our copy does not establish Hyr1’s contribution to virulence in disseminated candidiasis or address whether its host-cell receptor was unknown. (LLM, conf=0.87)
Experimental — accuracy not yet measuredHyr1 is required for maximal virulence in an immunosuppressed mouse model of OPC.
“It has previously been found that Hyr1 also required for maximal virulence in an immunosuppressed mouse model of OPC [25].”
From Candida albicans stimulates formation of a multi-receptor complex that mediates epithelial cell invasion during oropharyngeal infection (2023) · cites this paper as [25]
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Molecular Determinants Involved in Candida albicans Biofilm Formation and Regulation
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Powder diet exacerbates oropharyngeal candidiasis in a mouse model
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CANDIDA YEASTS AND CARCINOGENIC ACETALDEHYDE IN UPPER DIGESTIVE TRACT CARCINOGENESIS
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- Authors
- Dwivedi, P., Thompson, A., Xie, Z., Kashleva, H., Ganguly, S., Mitchell, A. P., & Dongari-Bagtzoglou, A.
- Affiliations
- University of Connecticut (US)
- Carnegie Mellon University (US)
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-01-25
- Volume
- 6
- Issue
- 1
- Pages
- e16218
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3026825
- OpenAlex
- W2091452473
- Cited by
- 110
- References
- 42
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 10 · 2023: 11 · 2022: 5 · 2021: 6 · 2020: 2 · 2019: 6 · 2018: 8 · 2017: 12 · 2016: 7 · 2015: 4 · 2014: 6 · 2013: 9 · 2012: 12
- FWCI
- 6.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R01AI067703)
- National Institute of Dental and Craniofacial Research (R01DE013986)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Keywords
- Candida albicans, HWP1, fungal virulence, oropharyngeal infection, immunodeficient mice, pseudomembranous candidiasis
- MeSH terms
- Animals, Candida albicans, Fungal Proteins, Membrane Glycoproteins, Mouth Mucosa, Neutrophils, Transcription Factors, Biofilms, Adhesins, Bacterial, Mice, Immune Evasion
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