The Role of Nutritional Environment in Cryptococcus gattii Titan Cells' Ultrastructure, Biophysical Properties, Molecular Features, and Virulence in Cryptococcosis.

Background/objectives: Cryptococcus gattii presents a significant threat to healthy individuals. Titan cell formation, a key virulence factor, is influenced by the nutritional environment and plays a critical role in immune evasion and stress resistance. This study investigates the molecular and biophysical changes in titanized C. gattii cells grown in nutrient-rich Neurobasal™ medium, a potent inducer of titan cells.

Methods: An integrative approach was used, combining scanning electron microscopy, optical tweezers, fluorescence microscopy, and physicochemical methods to analyze C. gattii cells grown in Neurobasal™ medium and minimal media.

Results: Cells grown in Neurobasal™ medium exhibited significant differences compared to those grown in minimal media. These included a thicker and more defined polysaccharide capsule, enhanced capsule elasticity, and the secretion of more elastic polysaccharides. Furthermore, cells grown in the enriched medium showed reduced susceptibility to antifungals and delayed mortality in infection models.

Conclusions: C. gattii adapts to nutritional cues by forming titan cells, thereby enhancing its pathogenicity. Targeting nutritional sensing pathways may offer novel therapeutic strategies against cryptococcal infections.