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Protein kinase A governs growth and virulence in Candida tropicalis

Chi-Jan Lin1, Chia-Yen Wu1, Shang-Jie Yu1

  • 1a Department of Plant Pathology and Microbiology , National Taiwan University , Taipei , Taiwan.

Virulence
|December 20, 2017
PubMed

Insights

The protein kinase A (PKA) pathway is crucial for Candida tropicalis virulence. Tpk1 regulates drug tolerance and cell wall integrity, while Tpk2 controls dimorphism and adhesion, with both essential for growth and infection.

Area of Science:

  • Medical Mycology
  • Molecular Biology
  • Pathogen Virulence

Background:

  • Candida tropicalis is a significant human fungal pathogen causing superficial and systemic infections.
  • The cyclic AMP/protein kinase A (cAMP/PKA) pathway regulates virulence factors like adhesion and dimorphism in Candida albicans.
  • Limited research exists on the PKA pathway's role in Candida tropicalis.

Purpose of the Study:

  • To investigate the roles of Tpk1 and Tpk2, the catalytic subunits of PKA, in Candida tropicalis.
  • To determine their involvement in fungal growth, cell wall integrity, drug tolerance, and virulence.

Main Methods:

  • Gene deletion to create tpk1/tpk1, tpk2/tpk2, and tpk1/tpk1 tpk2/tpk2 mutants.
  • Assessment of hyphal growth, adhesion, and biofilm formation.
  • Evaluation of virulence in a murine model of systemic infection.
  • Analysis of gene expression for virulence factors (EFG1, HWP1, BCR1, FLO8, GAL4, RIM101).

Main Results:

  • Tpk1 is involved in cell wall integrity and drug tolerance.
  • tpk2/tpk2 mutants exhibited reduced hyphal growth and adhesion.
  • The double deletion mutant showed delayed growth and impaired hyphal formation.
  • Both TPK1 and TPK2 are essential for full virulence in a systemic infection model.
  • PKA regulates EFG1 and HWP1 expression, while BCR1, FLO8, GAL4, and RIM101 are upregulated in the double mutant.

Conclusions:

  • Tpk1 plays a role in drug tolerance and cell wall integrity in C. tropicalis.
  • Tpk2 is a key regulator of dimorphism and adhesion.
  • Both Tpk1 and Tpk2 are necessary for C. tropicalis growth and virulence.
Keywords:
C. tropicalisPKAadhesionhyphal growthvirulence

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