Repositioning Antimicrobial Peptides Against WHO-Priority Fungi.

Area of Science:

• Mycology
• Infectious Diseases
• Biotechnology

Background:

• Rising threat of invasive fungal infections, especially in immunocompromised patients.
• Limited antifungal drug options and increasing resistance necessitate novel therapeutic strategies.
• World Health Organization identified key fungal pathogens like Candida auris and Aspergillus fumigatus due to resistance and virulence.

Purpose of the Study:

• To review and analyze antimicrobial peptide (AMP)-based strategies against critical fungal pathogens.
• To explore advancements in AMP molecular engineering and targeted delivery systems.
• To discuss the potential of AMPs as next-generation antifungal therapeutics.

Main Methods:

• Analysis of structure-activity relationships for AMP optimization.
• Review of molecular engineering techniques: hybridization, cyclization, PEGylation, and nanoparticle conjugation.
• Examination of computational approaches, including machine learning, for rational AMP design.

Main Results:

• AMPs demonstrate broad-spectrum activity and rapid membrane-disrupting mechanisms with low resistance potential.
• Engineered AMPs show enhanced stability, specificity, and pharmacokinetic properties.
• Multidisciplinary advances highlight AMPs' potential against multidrug-resistant fungi.

Conclusions:

• Antimicrobial peptides represent a promising avenue for next-generation antifungal therapies.
• Further research and investment in formulation, regulatory processes, and clinical translation are crucial for AMPs' success.