Cited by 121Fungal and yeast genetics researchAntifungal resistance and susceptibilityFungal Infections and Studies

Calcineurin Is Essential for Virulence in Candida albicans

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Bader, Teresa, Bodendorfer, Barbara, Schröppel, Klaus, Morschhäuser, Joachim·2003·Infection and Immunity

Abstract

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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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
Published
2003-09
Volume
71
Issue
9
Pages
5344-5354
ISSN
  • 0019-9567 (ISSN-L)
  • 1098-5522
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
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 › Epidemiology › 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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