Exploring fungal survival mechanisms: toward next-generation antifungal therapies against Candida spp.

Candida Spp are predominant opportunistic fungal pathogens responsible for a broad spectrum of infections, ranging from superficial mucosal candidiasis to life-threatening systemic diseases, particularly in immunocompromised individuals. Its complex biology and adaptive mechanisms contribute to pathogenicity and antifungal resistance, presenting significant therapeutic challenges. This review aimed to explore fungal survival mechanisms that can be exploited for the development of antifungal drugs. Key structural drug target components include the fungal cell wall, comprising β-glucan, chitin, and the plasma membrane, as well as ergosterol, which serve as critical targets for antifungal intervention. Biosynthesis inhibitors show promise in compromising cell integrity. Biofilm formation, driven by quorum sensing and extracellular matrix production, further enhances resistance to antifungal agents and host immune responses. Virulence factors, including hyphal wall protein 1, secreted aspartyl proteinases, and phospholipases, facilitate adhesion, invasion, and immune modulation, making them attractive targets for therapeutic development. Additionally, stress response pathways, such as the Hsp90 calcineurin axis and oxidative stress regulators, offer novel avenues for developing new antifungal treatments. Metabolic flexibility, involving amino acid biosynthesis and the glyoxylate cycle, underpins fungal adaptation to the host environment and presents further opportunities for targeted intervention. This review explores the multifaceted survival strategies of Candida Spp. and highlights molecular pathways that can be exploited for antifungal drug development. Advancing our understanding of these mechanisms is crucial for the development of next-generation therapeutics that aim to overcome resistance, enhance treatment efficacy, and improve patient outcomes. A multidisciplinary approach integrating molecular biology, pharmacology, and clinical sciences is vital for translating these insights into effective antifungal strategies.