Dermatophytic defensin with antiinfective potential

Area of Science:

• Microbiology
• Biochemistry
• Pharmacology

Background:

• Fungi are an emerging source of novel peptide antibiotics.
• Fungal defensin-like peptides (fDLPs) represent a promising class of antimicrobial agents.

Purpose of the Study:

• To identify and characterize new fDLPs from fungal genomes.
• To evaluate the therapeutic potential of a specific fDLP, micasin, against pathogenic bacteria.

Main Methods:

• Identification of 17 new fDLP genes.
• Structural analysis of synthetic micasin using Nuclear Magnetic Resonance (NMR).
• Assessment of micasin's antibacterial activity, mechanism of action, hemolysis, and serum stability.
• Evaluation of micasin's efficacy in a murine peritonitis model.

Main Results:

• Synthetic micasin adopts a characteristic cysteine-stabilized α-helical and β-sheet fold.
• Micasin exhibits potent activity against Gram-positive and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa.
• Micasin demonstrates rapid bacterial killing via a non-disruptive membrane mechanism, with low hemolysis and high serum stability.
• Micasin significantly improves survival rates in a mouse model of bacterial peritonitis.

Conclusions:

• Fungal genomes are a valuable resource for discovering novel peptide antibiotics.
• Micasin is a promising candidate for further development as a therapeutic antimicrobial agent.
• The study validates a strategy for exploring fungal-derived peptides for drug discovery.