Breaking the Barrier: Cutting-Edge Microbial Strategies Against Candida Biofilm Infections

Candida species, particularly Candida albicans and nonalbicans, can form strong biofilms on biotic and abiotic surfaces, leading to chronic and recurring infections. These biofilms are influenced by regulatory circuits, transcription factors, and morphogenetic changes that promote biofilm development and drug resistance. The biofilm matrix, including β-glucans and extracellular DNA, hinders antifungal penetration. Next-generation approaches to controlling Candida biofilms include small-molecule inhibitors, quorum-sensing inhibitors, enzyme-based ECM inhibitors, and nanoparticle-mediated drug delivery platforms. Marine-derived metabolites, antimicrobial peptides, and monoclonal antibodies are also discussed for their antibiofilm activity. Innovative in vitro and in vivo models are presented for assessing biofilm behavior and treatment response. Polymicrobial biofilms, including Candida and bacteria, are also discussed. Obstacles to controlling Candida biofilms include antifungal resistance, therapeutic agent toxicity, and regulatory hurdles. Future directions include CRISPR-based gene editing, antifungal vaccines, and omics-based target identification. This review emphasizes the importance of multidisciplinary, biofilm-centric therapeutic strategies in reducing the global health impact of Candida biofilm-related infections and advancing innovative antifungal therapies.