Molecular Triggers of Yeast Pathogenicity in the Yeast–Host Interactions

Abstract

Candida and other pathogenic yeast species, able to transition from non-invasive commensal organisms to invasive pathogens, are characterized by a high ability to adapt to stress conditions encountered in the human host, such as pH and temperature shifts, CO2 and oxygen level variations, and nutritional limitations. Although Candida albicans remains the main cause of Candida-related infections, non-albicans Candida (NAC) species, including C. tropicalis, C. parapsilosis, C. krusei, and non-Candida species such as Yarrowia lipolytica, Candidozyma auris, and Nakaseomyces glabratus, are gaining clinical importance. These species exhibit diverse mechanisms of pathogenicity, including morphological transition, modulation of gene expression pathways (cAMP-PKA/MAPK, Hsp, calcineurin, GlcNAc-mediated signaling), cell wall remodeling, post-translational reprogramming, biofilm formation, antifungal resistance, and enzyme secretion. C. albicans exhibits high morphological and metabolic plasticity for survival across body niches. N. glabratus and C. tropicalis show strong azole resistance and biofilm formation, while C. parapsilosis and C. krusei pose risks through surface adhesion and treatment resistance. C. auris stands out for heat tolerance, multidrug resistance, and outbreak potential. Y. lipolytica, though rare, forms persistent filamentous biofilms in critical care settings. Cryptococcus neoformans remains a life-threatening pathogen capable of immune evasion and crossing the blood–brain barrier. This review compares molecular mechanisms of pathogenicity across these fungi, emphasizing environmental adaptation, conserved and species-specific responses, and potentially highlighting targets for therapeutic management.