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DYRK-family kinases regulate Candida albicans morphogenesis and virulence through the Ras1/PKA pathway.
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ABSTRACT: Importance
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.
SUBMITTER: MacAlpine J
PROVIDER: S-EPMC10746247 | biostudies-literature | 2023 Nov
REPOSITORIES: biostudies-literature
Publications
DYRK-family kinases regulate <i>Candida albicans</i> morphogenesis and virulence through the Ras1/PKA pathway.
mBio 20231128 6
<h4>Importance</h4><i>Candida albicans</i> 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 <i>C. albicans</i> filamentation. Here, we demonstrate that Yak1 regulates morphogenesis through the canonical cAMP/PKA pathway ...[more]