Candida albicans hyphal initiation and elongation

•Hyphal development requires two phases of regulation to remove Nrg1 inhibition.•Nrg1 removal upon activation of cAMP and release from farnesol initiate hyphal growth.•Chromatin regulation and Ume6 stability act in parallel for hyphal elongation in vivo.•Hyphal initiation and maintenance are temporally linked.

The fungus Candida albicans is a benign member of the mucosal microbiota, but can cause mucosal infections and life-threatening disseminated invasive infections in susceptible individuals. The ability to switch between yeast, pseudohyphal, and hyphal growth forms (polymorphism) is one of the most investigated virulence attributes of C. albicans. Recent studies suggest that hyphal development in C. albicans requires two temporally linked regulations for initiation and maintenance of the hyphal transcriptional program. Hyphal initiation requires a rapid but temporary disappearance of the Nrg1 transcriptional repressor of hyphal morphogenesis. Hyphal maintenance requires active sensing of the surrounding environment, leading to exclusion of Nrg1 binding to promoters of hypha-specific genes or reduced NRG1 expression. We discuss recent advances in understanding the complex transcriptional regulation of hyphal gene expression. These provide molecular mechanisms underpinning the phenotypic plasticity of C. albicans polymorphism.