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Regulation of the Candida albicans cell wall damage response by transcription factor Sko1 and PAS kinase Psk1

Jason M Rauceo1, Jill R Blankenship, Saranna Fanning

  • 1Department of Microbiology and Institute of Cancer Research, Columbia University, New York, NY 10032, USA.

Molecular Biology of the Cell
|April 25, 2008
PubMed

Insights

Candida albicans transcription factor SKO1 is crucial for cell wall integrity and responding to caspofungin, an antifungal drug. A newly identified pathway involving protein kinase Psk1 regulates SKO1 function.

Area of Science:

  • Mycology
  • Molecular Biology
  • Cell Biology

Background:

  • Fungal cell wall integrity is vital for survival in diverse environments.
  • Regulatory pathways governing cell wall composition can diverge significantly between fungal species.
  • Caspofungin, a beta-1,3-glucan synthase inhibitor, targets fungal cell wall synthesis.

Purpose of the Study:

  • To investigate the role of transcription factor SKO1 in Candida albicans response to cell wall stress.
  • To elucidate the signaling pathway regulating SKO1 function under caspofungin treatment.

Main Methods:

  • Analysis of Candida albicans transcription factor mutants, specifically SKO1.
  • Phenotypic characterization of caspofungin sensitivity in wild-type and mutant strains.
  • Investigation of Hog1-dependent phosphorylation and SKO1 transcript levels under osmotic stress and caspofungin exposure.
  • Identification of upstream regulators through protein kinase-defective mutants.

Main Results:

  • Mutations in SKO1 confer hypersensitivity to caspofungin.
  • Unlike osmotic stress, Sko1 is not phosphorylated in response to caspofungin, indicating a distinct regulatory mechanism.
  • SKO1 transcript levels are induced by caspofungin.
  • SKO1 is essential for the expression of caspofungin-inducible genes.
  • Protein kinase Psk1 is required for SKO1 expression and function in response to caspofungin.

Conclusions:

  • The Hog1-Sko1 phosphorylation axis is conserved for osmotic stress response.
  • Sko1 plays a critical, non-phosphorylated role in mediating the response to caspofungin-induced cell wall stress.
  • A novel signal transduction pathway involving Psk1 and Sko1 regulates fungal cell wall integrity against caspofungin.

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