Shape-Shifting Mechanisms: Integrative Multi-Omics Insights Into Candida albicans Morphogenesis

The ability of Candida albicans to switch among yeast, hyphal, and pseudohyphal forms underlies its adaptability and pathogenicity. While cAMP-dependent signaling has long been considered central to hyphal growth, recent multi-omics studies show that cAMP-independent mechanisms also drive morphological changes. Basal PKA activity, cyclin-dependent kinases (e.g., Cdc28), and other regulators can promote shape-shifting even without classical cAMP pathways. In addition, N-acetylglucosamine (GlcNAc) acts as a potent signal that induces hyphal growth independently of its metabolic role, directly connecting environmental cues to morphological states. By integrating transcriptomic, proteomic, and phosphoproteomic data, this review exposes the intricate networks controlling C. albicans morphogenesis. A clearer understanding of these complex regulatory circuits lays the groundwork for future studies that employ advanced multi-omics analyses. Such approaches will help elucidate how these pathways converge, how they respond to changing environments, and how they might be harnessed or disrupted to influence fungal behavior.