Molecular mechanisms, pathogenesis and therapeutic advances of Candida albicans in oral candidiasis

Oral candidiasis (OC), caused mainly by Candida albicans , is a common opportunistic fungal infection and typically affects immunocompromised individuals. The rise in antifungal resistance, biofilm-associated persistence, and immune evasion mechanisms has complicated OC management. This review examines in depth the molecular pathogenesis of C. albicans in OC, including virulence factors associated with adhesion, morphogenesis, quorum sensing, immune evasion, and biofilm formation. The review highlights the central roles of the cAMP-PKA, MAPK, Rim101, and TOR signaling pathways in regulating yeast-to-hyphal transition, virulence, stress adaptation, and biofilm development. In particular, dysregulation of these pathways promotes filamentation and biofilm maturation, contributing to persistent infection and reduced antifungal susceptibility. Conventional antifungal therapies, including azoles, polyenes, and echinocandins, remain important for OC management; however, biofilm-associated tolerance and emerging resistance can limit their effectiveness, emphasizing the need for complementary therapeutic approaches. Emerging strategies, including host-directed therapies, probiotics, photodynamic therapy (PDT), phytotherapeutics, essential oils, phenolic compounds, nanoparticles, and antimicrobial peptides, show promising antibiofilm and adjunctive potential. Clinical and experimental evidence indicates that PDT can reduce Candida burden, while probiotics may reduce oral Candida colonization and interfere with biofilm development. Furthermore, natural products, nanoparticles, and antimicrobial peptides may enhance conventional antifungal activity through complementary mechanisms. The reviewed evidence suggests that targeting fungal virulence and biofilm-associated mechanisms alongside conventional antifungal therapy may provide a more effective strategy for recurrent and drug-resistant OC. Future research should prioritize standardized clinical evaluation of antibiofilm therapies, microbiome-directed interventions, personalized treatment approaches, and combination therapies to improve therapeutic outcomes.