Calcineurin is essential for Candida albicans survival in serum and virulence

Jill R. Blankenship, Floyd L. Wormley, Molly K. Boyce, Wiley A. Schell, Scott G. Filler, John R. Perfect, Joseph Heitman

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

Calcineurin is a calcium-activated protein phosphatase that is the target of the immunosuppressants cyclosporin A and FK506. In T cells, calcineurin controls nuclear import of the NF-AT transcription factor and gene activation. In plants and fungi, calcineurin functions in stress responses (e.g., temperature, cations, and pH) and is necessary for the virulence of the fungal pathogen Cryptococcus neoformans. Here we show that calcineurin is also required for the virulence of another major fungus that is pathogenic to humans, Candida albicans. C. albicans calcineurin mutants had significantly reduced virulence in a murine model of systemic infection. In contrast to its role in C. neoformans, calcineurin was not required for C. albicans survival at 37°C. Moreover, C. albicans calcineurin mutant strains exhibited no defects in known Candida virulence traits associated with host invasion, including filamentous growth, germ tube formation, and adherence to and injury of mammalian cells. C. albicans calcineurin mutant strains failed to colonize and grow in the kidneys of infected animals and were unable to survive when exposed to serum in vitro. Our studies illustrate that calcineurin has evolved to control aspects of the virulence of two divergent fungal pathogens via distinct mechanisms that can be targeted to achieve broad-spectrum antifungal action.

Original languageEnglish (US)
Pages (from-to)422-430
Number of pages9
JournalEukaryotic Cell
Volume2
Issue number3
DOIs
StatePublished - Jun 1 2003

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Calcineurin
Candida albicans
Virulence
virulence
Serum
Cryptococcus neoformans
mutants
immunosuppressive agents
fungi
cyclosporine
gene activation
germ tube
pathogens
Candida
Transcriptional Activation
imports
Fungi
stress response
cations
transcription factors

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Cite this

Blankenship, J. R., Wormley, F. L., Boyce, M. K., Schell, W. A., Filler, S. G., Perfect, J. R., & Heitman, J. (2003). Calcineurin is essential for Candida albicans survival in serum and virulence. Eukaryotic Cell, 2(3), 422-430. https://doi.org/10.1128/EC.2.3.422-430.2003

Calcineurin is essential for Candida albicans survival in serum and virulence. / Blankenship, Jill R.; Wormley, Floyd L.; Boyce, Molly K.; Schell, Wiley A.; Filler, Scott G.; Perfect, John R.; Heitman, Joseph.

In: Eukaryotic Cell, Vol. 2, No. 3, 01.06.2003, p. 422-430.

Research output: Contribution to journalArticle

Blankenship, JR, Wormley, FL, Boyce, MK, Schell, WA, Filler, SG, Perfect, JR & Heitman, J 2003, 'Calcineurin is essential for Candida albicans survival in serum and virulence', Eukaryotic Cell, vol. 2, no. 3, pp. 422-430. https://doi.org/10.1128/EC.2.3.422-430.2003
Blankenship, Jill R. ; Wormley, Floyd L. ; Boyce, Molly K. ; Schell, Wiley A. ; Filler, Scott G. ; Perfect, John R. ; Heitman, Joseph. / Calcineurin is essential for Candida albicans survival in serum and virulence. In: Eukaryotic Cell. 2003 ; Vol. 2, No. 3. pp. 422-430.
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