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DYRK-family kinases regulate Candida albicans morphogenesis and virulence through the Ras1/PKA pathway

Jessie MacAlpine1, Zhongle Liu1, Saif Hossain1

  • 1Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.

Mbio
|November 28, 2023
PubMed
Abstract

Insights

Candida albicans filamentation, a key virulence trait, is regulated by the kinase Yak1. Host CO2 levels can bypass Yak1

Area of Science:

  • Mycology
  • Molecular Biology
  • Infectious Diseases

Background:

  • Candida albicans is an opportunistic fungal pathogen causing severe infections in immunocompromised individuals.
  • Fungal morphogenesis, specifically yeast-to-filament transition, is a critical virulence factor.
  • The kinase Yak1 has been previously implicated in regulating C. albicans filamentation.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which Yak1 regulates C. albicans morphogenesis.
  • To investigate the role of environmental factors, such as CO2 concentration, in Yak1-mediated filamentation.
  • To assess the in vivo relevance of Yak1 in a C. albicans infection model.

Main Methods:

  • Genetic manipulation of C. albicans, including gene deletion of Yak1 and Pom1.
  • Analysis of fungal morphology under varying CO2 concentrations and through the cAMP/PKA pathway.
  • In vivo studies using a mouse model of C. albicans dermatitis.

Main Results:

  • Yak1 regulates C. albicans morphogenesis via the canonical cAMP/PKA pathway.
  • Host-relevant CO2 concentrations bypass the requirement for Yak1 in filamentation.
  • The kinase Pom1 compensates for Yak1 loss under host-relevant conditions; double mutants are non-filamentous.

Conclusions:

  • Yak1 is a key regulator of C. albicans virulence, modulated by environmental cues like CO2.
  • Understanding Yak1's regulation provides insights into fungal pathogenesis and potential therapeutic targets.
  • Yak1 is essential for C. albicans filamentation during experimental dermatitis.
Keywords:
Candida albicansDYRKRas1/PKAYak1 kinasedermatitisfungal pathogenmorphogenesis

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