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Candida albicans protein kinase CK2 governs virulence during oropharyngeal candidiasis

Lisa Y Chiang1, Donald C Sheppard, Vincent M Bruno

  • 1Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.

Cellular Microbiology
|August 31, 2006
PubMed

Insights

The protein kinase CK2 catalytic subunit Cka2p is crucial for Candida albicans interactions with host cells and virulence in oropharyngeal candidiasis. Loss of Cka2p impairs damage to endothelial and oral epithelial cells, and reduces invasion of oral cells.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Infectious Diseases

Background:

  • Candida albicans is an opportunistic fungal pathogen responsible for various infections.
  • Understanding host-pathogen interactions is critical for developing effective antifungal therapies.

Purpose of the Study:

  • To identify Candida albicans genes essential for host cell interactions and virulence.
  • To investigate the role of protein kinase CK2 subunits in C. albicans pathogenesis.

Main Methods:

  • Screening of C. albicans insertion mutants for reduced endothelial cell damage.
  • Construction and characterization of cka2delta/cka2delta and cka1delta/cka1delta mutant strains.
  • Assessment of in vitro endothelial and oral epithelial cell damage and invasion.
  • Evaluation of virulence in mouse models of disseminated and oropharyngeal candidiasis.

Main Results:

  • CKA2, encoding a catalytic subunit of protein kinase CK2, was identified as crucial.
  • cka2delta/cka2delta mutants showed reduced damage to endothelial and oral epithelial cells, and defective oral epithelial cell invasion.
  • These mutants were hypersusceptible to hydrogen peroxide but not to salt or cell wall agents.
  • While cka1delta/cka1delta mutants showed no defects, CKA1 overexpression in cka2delta/cka2delta restored wild-type phenotypes.
  • cka2delta/cka2delta mutants exhibited normal virulence in disseminated candidiasis but attenuated virulence in oropharyngeal candidiasis.

Conclusions:

  • Cka2p plays a significant role in mediating C. albicans interactions with host cells in vitro.
  • Cka2p is essential for C. albicans virulence during oropharyngeal candidiasis.
  • Protein kinase CK2 is a key regulator of C. albicans pathogenesis, particularly in mucosal infections.

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