Antifungal Peptides (AFPs) show promise for disrupting drug-resistant fungal biofilms by diverse mechanisms

Invasive fungal infections in intensive care units pose a severe threat, particularly when complicated by biofilm formation. These biofilms render fungi highly resistant to conventional antifungal drugs and evade host immune responses, leading to high mortality rates. Pathogens like Candida auris, Candida albicans, and Aspergillus fumigatus are notorious for developing multidrug resistance and causing persistent infections in critically ill patients. Standard antifungal treatments often fail against these resilient biofilms, necessitating novel therapeutic strategies. Antifungal peptides (AFPs), either naturally derived or rationally designed, are emerging as a promising avenue to overcome this critical treatment gap.

This review synthesizes current research on antifungal peptides (AFPs) as a promising therapeutic strategy for biofilm-associated fungal infections. It systematically explores the diverse mechanisms AFPs employ, such as cell membrane disruption, inhibition of fungal adhesion and morphogenesis, and degradation of the extracellular matrix. The review also examines advanced peptide engineering and delivery methods, including nanocarriers and hydrogel systems, designed to improve AFP stability and targeted efficacy against biofilms. Additionally, it discusses the potential for AFPs to act synergistically with conventional antifungal drugs, addressing the critical challenge of multidrug resistance.

Antifungal peptides (AFPs) demonstrate multiple potent mechanisms against fungal biofilms. They primarily act by directly disrupting the fungal cell membrane, leading to cell lysis. AFPs also effectively block early fungal adhesion and morphogenesis, preventing biofilm initiation and development. Furthermore, they contribute to weakening the biofilm's extracellular matrix, making established biofilms more vulnerable. > Importantly, AFPs show significant potential for synergistic action with existing antifungal drugs, enhancing overall treatment efficacy against drug-resistant strains. Recent advancements in peptide engineering have improved AFP stability and selectivity, while novel delivery methods, such as nanocarriers and hydrogel-based systems, have enhanced their ability to target fungal biofilms in experimental models. These innovations address key pharmacokinetic limitations, paving the way for more effective localized delivery and sustained release. The review highlights that AFPs represent a rapidly evolving research area with substantial promise for overcoming the challenges posed by persistent, drug-resistant fungal infections.