Phospho-regulation of Fkh2 in Candida albicans

The opportunistic human fungal pathogen, Candida albicans, undergoes morphological and transcriptional adaptation in the switch from commensalism to pathogenicity. Previous research on this switch has focused on genes involved in the morphological switch from yeast to hyphal growth. However, very few genes have been found that directly control hyphal morphogenesis, suggesting primary control at the post‐translational level. The Cyclin Dependent Kinases (CDK), Cdk1, has been previously implicated in this process; therefore it was sought to identify phospho­‐regulatory targets of Cdk1 involved in C. albicans hyphal morphogenesis. Fkh2 was a likely CDK target that shows differential phosphorylation between yeast and hyphal growth; being phosphorylated in conjunction with cell cycle progression during yeast growth, but not in hyphae, where phosphorylation occurs for a short period on hyphal induction. Further investigations have found that Fkh2 is phosphorylated at C-­‐terminal CDK consensus sites on hyphal induction, but is not a regulatory target of Cdk1, or any other CDK related protein present in C. albicans. Although the kinase responsible remains elusive, the physiological consequences of the phosphorylation have been found to be quite profound, with phosphorylation of Fkh2 being a requirement for the maintenance of invasive filamentous growth. Loss of Fkh2 phosphorylation specifically prevents the expression of genes required for: filamentous growth, pathogenesis, host interaction and biofilm formation, which are required for the transition from commensalism to pathogenesis. Thus phosphorylation of Fkh2 on hyphal induction provides a cell cycle­‐independent function that contributes to pathogenesis.