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Calcineurin Is Essential for Virulence in Candida albicans
Open accessAbstract
Calcineurin is a conserved Ca 2+ -calmodulin-activated, serine/threonine-specific protein phosphatase that regulates a variety of physiological processes, e.g., cell cycle progression, polarized growth, and adaptation to salt and alkaline pH stresses. In the pathogenic yeast Cryptococcus neoformans , calcineurin is also essential for growth at 37°C and virulence. To investigate whether calcineurin plays a role in the virulence of Candida albicans , the major fungal pathogen of humans, we constructed C. albicans mutants in which both alleles of the CMP1 gene, encoding the calcineurin catalytic subunit, were deleted. The C. albicans Δ cmp1 mutants displayed hypersensitivity to elevated Na + , Li + , and Mn 2+ concentrations and to alkaline pH, phenotypes that have been described after calcineurin inactivation in the related yeast Saccharomyces cerevisiae . Unlike S. cerevisiae calcineurin mutants, which exhibit reduced susceptibility to high Ca 2+ concentrations, growth of C. albicans was inhibited in the presence of 300 mM CaCl 2 after the deletion of CMP1 , demonstrating that there are also differences in calcineurin-mediated cellular responses between these two yeast species. In contrast to C. neoformans , inactivation of calcineurin did not cause temperature sensitivity in C. albicans . In addition, hyphal growth, an important virulence attribute of C. albicans , was not impaired in the Δ cmp1 mutants under a variety of inducing conditions. Nevertheless, the virulence of the mutants was strongly attenuated in a mouse model of systemic candidiasis, demonstrating that calcineurin signaling is essential for virulence in C. albicans .
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“For example, the observed C. glabrata Δcnb1 strain phenotype, which is characterized by an increased susceptibility to azoles and cell wall-damaging agents as well as decreased virulence, is consistent with previous findings for other pathogenic fungi, such as C. albicans (2-4, 27), C. neoformans (11, 18, 21), and A. fumigatus (9, 30).”
From Roles of Calcineurin and Crz1 in Antifungal Susceptibility and Virulence of Candida glabrata (2010) · cites this paper as [2]
In the citing paper
“Also these mutants show hypersensitivity to agents causing cell wall damage or perturbing cell membrane integrity including some antifungals.”
From Functional characterization of the Candida albicans CRZ1 gene encoding a calcineurin-regulated transcription factor (2005) · cites this paper as Bader et al. 2003
In the citing paper
“Calcineurin has been shown to be essential for C. albicans survival in serum and virulence in a murine model of infection, but the molecular mechanisms involved are still unknown (Blankenship et al. 2003;Bader et al. 2003;Sanglard et al. 2003).”
From Functional characterization of the Candida albicans CRZ1 gene encoding a calcineurin-regulated transcription factor (2005) · cites this paper as Bader et al. 2003
In the citing paper
“C. albicans mutants lacking either one of the calcineurin subunits are viable but exhibit increased sensitivity to ionic stress conditions (Cruz et al. 2002;Sanglard et al. 2003;Bader et al. 2003).”
From Functional characterization of the Candida albicans CRZ1 gene encoding a calcineurin-regulated transcription factor (2005) · cites this paper as Bader et al. 2003
In the citing paper
“The C. albicans cna1/cna1 and cmp1/cmp1 strains, having deleted the calcineurin catalytic subunit, exhibit increased susceptibility to alkaline cation toxicity (Sanglard et al. 2003;Bader et al. 2003).”
From Functional characterization of the Candida albicans CRZ1 gene encoding a calcineurin-regulated transcription factor (2005) · cites this paper as Bader et al. 2003
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Metadata
- Authors
- Bader, T., Bodendorfer, B., Schröppel, K., & Morschhäuser, J.
- Affiliations
- University of Würzburg (DE)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Institut für Klinische Mikrobiologie, Immunologie und Hygiene, Universität Erlangen, D-91054 Erlangen
- Institut für Molekulare Infektionsbiologie, Universität Würzburg, D-97070 Würzburg
- Venue
- Infection and Immunity
- Publisher
- American Society for Microbiology
- Published
- 2003-09
- Volume
- 71
- Issue
- 9
- Pages
- 5344-5354
- ISSN
- 0019-9567 (ISSN-L)
- 1098-5522
- PMC
- PMC187310
- OpenAlex
- W2149198831
- Cited by
- 121
- References
- 52
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 4 · 2023: 1 · 2022: 3 · 2021: 5 · 2020: 5 · 2019: 5 · 2018: 1 · 2017: 8 · 2016: 5 · 2015: 6 · 2014: 9 · 2013: 5 · 2012: 5
- FWCI
- 2.07
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Infection and Immunity (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Burroughs Wellcome Fund
- Deutsche Forschungsgemeinschaft
- Bayerische Forschungsstiftung
- 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 › Infectious Diseases › Fungal Infections and Studies
- Keywords
- calcineurin, Candida albicans, virulence, systemic candidiasis, hyphal growth, cation sensitivity, temperature sensitivity, protein phosphatase, mouse model, Cryptococcus neoformans
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Candida albicans, Candidiasis, DNA, Fungal, Female, Genes, Fungal, Humans, Hydrogen-Ion Concentration, Mice, Inbred BALB C, Molecular Sequence Data, Virulence, Gene Deletion, Sequence Homology, Amino Acid, Calcineurin, Protein Subunits, Mice
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