Self-Assembling Nano-Antimicrobial Oligopeptides With Dual Offense-Defense Functions for Synchronously Achieving High...

Area of Science:

• Biotechnology
• Materials Science
• Infectious Diseases

Background:

• Self-assembling nano-antimicrobial peptides (nano-AMPs) show potential against antibiotic-resistant bacteria.
• A key challenge is the activity-biocompatibility paradox, limiting their therapeutic application.
• Developing nano-AMPs with selective toxicity is crucial for effective antimicrobial strategies.

Purpose of the Study:

• To design nano-AMPs with an "integrated offense-defense" strategy.
• To decouple antimicrobial potency from host cytotoxicity by inhibiting mammalian cell binding and enhancing bacterial membrane insertion.
• To engineer nano-AMPs with optimized surface charge and molecular packing for improved efficacy and safety.

Main Methods:

• Systematic sequence engineering of peptide nanofibers.
• Experimental and theoretical analysis of nano-AMP interactions with bacterial and mammalian cell membranes.
• Evaluation of antimicrobial activity (MIC) and biosafety (therapeutic index, selectivity index).
• Assessment in a murine skin wound infection model.

Main Results:

• Nano-AMPs with moderate positive surface potentials (∼+20 mV) showed preferential binding to bacteria over mammalian cells.
• Engineered peptide nanofibers exhibited loose molecular packing and exposed hydrophobic residues.
• Optimized nano-AMPs demonstrated potent antimicrobial activity (MIC 5–6 µM) and high biosafety (TI > 30, SI > 50).
• In vivo studies confirmed reduced bacterial burden and accelerated wound healing.

Conclusions:

• The "integrated offense-defense" strategy successfully decouples nano-AMP antimicrobial activity from host cytotoxicity.
• Engineered nano-AMPs with specific surface charge and structure offer a promising solution for combating bacterial infections.
• These findings pave the way for developing safer and more effective antimicrobial peptide-based therapeutics.