Signaling Pathways Regulating Dimorphism in Medically Relevant Fungal Species

Pathogenic fungi exhibit morphological plasticity, a phenomenon known as dimorphism, which allows them to switch between yeast and hyphal forms in response to environmental stimuli. Thermodimorphic fungi undergo this transition based on temperature changes, playing a crucial role in their virulence and life cycle. Under saprobic conditions, some fungi exist as filamentous hyphae, producing conidia. When conidia are inhaled by mammals or traumatically inoculated body temperature (37°C) triggers their dimorphism into yeast cells. This shift promotes fungal dis-semination and immune evasion. Some fungal pathogens undergo dimorphism in the contrary way, forming pseudohyphae and hyphae within the host. While temperature is a major driver of di-morphism, other factors, including CO₂ concentration, pH, nitrogen sources, and quorum-sensing molecules, also contribute to morphological shifts. This morphological transition is associated with increased expression of virulence factors that aid in adhesion, colonization, and immune evasion. This review examines the signaling pathways regulating fungal dimorphism, focusing on H. cap-sulatum as a model for mycelium-to-yeast transitions and C. albicans for yeast-to-hypha transitions. Understanding these pathways is essential for advancing therapeutic approaches against systemic fungal infections.