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

mBio. 2023 Dec 19;14(6):e0218323. doi: 10.1128/mbio.02183-23. Epub 2023 Nov 28.

Abstract

Candida albicans is an opportunistic human fungal pathogen that frequently causes life-threatening infections in immunocompromised individuals. To cause disease, the fungus employs several virulence traits, including its ability to transition between yeast and filamentous states. Previous work identified a role for the kinase Yak1 in regulating C. albicans filamentation. Here, we demonstrate that Yak1 regulates morphogenesis through the canonical cAMP/PKA pathway and that this regulation is environmentally contingent, as host-relevant concentrations of CO2 bypass the requirement of Yak1 for C. albicans morphogenesis. We show a related kinase, Pom1, is important for filamentation in the absence of Yak1 under these host-relevant conditions, as deletion of both genes blocked filamentous growth under all conditions tested. Finally, we demonstrate that Yak1 is required for filamentation in a mouse model of C. albicans dermatitis using genetic and pharmacological approaches. Overall, our results expand our understanding of how Yak1 regulates an important virulence trait in C. albicans.

Keywords: Candida albicans; DYRK; Ras1/PKA; Yak1 kinase; dermatitis; fungal pathogen; morphogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Candida albicans* / enzymology
  • Candida albicans* / genetics
  • Candida albicans* / growth & development
  • Candida albicans* / metabolism
  • Candida albicans* / pathogenicity
  • Candidiasis* / microbiology
  • Cyclic AMP-Dependent Protein Kinases* / genetics
  • Cyclic AMP-Dependent Protein Kinases* / metabolism
  • Disease Models, Animal
  • Fungal Proteins* / genetics
  • Fungal Proteins* / metabolism
  • Gene Expression Regulation, Fungal
  • Hyphae / genetics
  • Hyphae / growth & development
  • Hyphae / metabolism
  • Mice
  • Morphogenesis*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Signal Transduction
  • Virulence
  • ras Proteins / genetics
  • ras Proteins / metabolism

Substances

  • Cyclic AMP-Dependent Protein Kinases
  • Fungal Proteins
  • Protein Serine-Threonine Kinases
  • ras Proteins