Candida albicans protein kinase CK2 governs virulence during oropharyngeal candidiasis
Abstract
To identify Candida albicans genes whose proteins are necessary for host cell interactions and virulence, a collection of C. albicans insertion mutants was screened for strains with reduced capacity to damage endothelial cells in vitro. This screen identified CKA2. CKA2 and its homologue CKA1 encode the catalytic subunits of the protein kinase CK2. cka2delta/cka2delta strains of C. albicans were constructed and found to have significantly reduced capacity to damage both endothelial cells and an oral epithelial cell line in vitro. Although these strains invaded endothelial cells similarly to the wild-type strain, they were defective in oral epithelial cell invasion. They were also hypersusceptible to hydrogen peroxide, but not to high salt or to cell wall damaging agents. A cka1delta/cka1delta mutant caused normal damage to both endothelial cells and oral epithelial cells, and it was not hypersusceptible to hydrogen peroxide. However, overexpression of CKA1 in a cka2delta/cka2delta strain restored wild-type phenotype. Although the cka2delta/cka2delta mutant had normal virulence in the mouse model of haematogenously disseminated candidiasis, it had significantly attenuated virulence in the mouse model of oropharyngeal candidiasis. Therefore, Cka2p governs the interactions of C. albicans with endothelial and oral epithelial cells in vitro and virulence during oropharyngeal candidiasis.
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Host cell invasion and damage are likely critical virulence attributes of C. albicans because mutants with defects in these processes in vitro are highly likely to have attenuated virulence in experimental animal models of hematogenously disseminated or oropharyngeal candidiasis.
“Host cell invasion and damage are likely critical virulence attributes of C. albicans because mutants with defects in these processes in vitro are highly likely to have attenuated virulence in experimental animal models of hematogenously disseminated or oropharyngeal candidiasis [5][6][7][8].”
From Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells (2007) · cites this paper as [8]
Cites
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“Adherence assay The adherence of the C. albicans strains to oral epithelial cells and endothelial cells was measured using a minor modification of our previously described assay (Sheppard et al., 2004).”
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- Authors
- Chiang, L. Y., Sheppard, D. C., Bruno, V. M., Mitchell, A. P., Edwards, J. E., & Filler, S. G.
- Affiliations
- The Lundquist Institute (US)
- McGill University (CA)
- Columbia University (US)
- University of California, Los Angeles (US)
- Venue
- Cellular Microbiology
- Publisher
- Hindawi Limited
- Published
- 2007-01
- Volume
- 9
- Issue
- 1
- Pages
- 233-245
- ISSN
- 1462-5814 (ISSN-L)
- 1462-5822
- OpenAlex
- W2090775633
- Cited by
- 59
- References
- 8
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 2 · 2017: 3 · 2015: 2 · 2014: 2 · 2013: 3 · 2012: 8
- FWCI
- 2.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cellular Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bristol-Myers Squibb
- Pfizer Pharmaceuticals
- National Cancer Institute
- National Institute of Allergy and Infectious Diseases (R01AI019990, R01AI050931, R01-AI19990, R01 AI 50931, R01AI054928)
- National Institute of Dental and Craniofacial Research (R01DE013974, R01DE017088, R01 DE 13974)
- National Center for Research Resources (M01RR000425, M01-RR00425)
- NIH Clinical Center
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Keywords
- Candida albicans, casein kinase 2, oropharyngeal candidiasis, virulence, endothelial injury, hydrogen peroxide susceptibility, insertion mutants, host-pathogen interaction
- MeSH terms
- Animals, Candida albicans, Candidiasis, Candidiasis, Oral, Epithelial Cells, Fungal Proteins, Humans, Male, Mice, Inbred BALB C, Mouth Mucosa, Oropharynx, Specific Pathogen-Free Organisms, Virulence, Gene Expression Regulation, Fungal, Mutagenesis, Insertional, Oxidative Stress, Models, Animal, Endothelial Cells, Cell Line, Tumor, Casein Kinase II, Mice
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