Antimicrobial Peptides as Eco-Innovative Therapeutics to Overcome Antifungal Pressure-Induced Resistance in Candida...

The emergence of Candida species as a significant cause of hospital-acquired infections poses a growing challenge in the clinical management of fungal diseases, driven by increasing antifungal resistance. Both intrinsic and acquired resistance mechanisms have been documented, often as a consequence of prolonged antifungal pressure, leading to treatment failures. This review explores the role of antimicrobial peptides (AMPs) as a potential solution to overcoming acquired resistance in Candida species, specifically targeting resistance pathways that bypass conventional antifungal treatments. AMPs act via multifaceted mechanisms, such as disrupting the fungal cell membrane, inducing mitochondrial dysfunction, and generating reactive oxygen species (ROS), which reduces the likelihood of resistance development. Furthermore, AMPs exhibit a lower propensity for resistance emergence compared to traditional antifungal drugs due to their rapid action and broad spectrum of activity. The review investigates the molecular mechanisms of acquired resistance in Candida, including genetic mutations and adaptations that occur under antifungal pressure, and discusses how AMPs can counteract these adaptive responses. It also addresses the challenges of scaling AMP production, including issues related to batch variability, cost, and metabolic stability. Industrial efforts to overcome these hurdles are examined that could enhance sustainability and cost-effectiveness. The review concludes by advocating for the use of AMPs as part of combination therapies to address the limitations of existing antifungal treatments, offering a promising alternative in the fight against multidrug-resistant Candida infections.