A sonosensitive diphenylalanine-based broad-spectrum antimicrobial peptide

Area of Science:

• Biochemistry
• Materials Science
• Microbiology

Background:

• Antimicrobial peptides (AMPs) often exhibit slow action, rapid degradation, toxicity, and complex structures.
• Existing treatments face challenges from antibiotic-resistant bacteria, necessitating novel therapeutic strategies.

Purpose of the Study:

• To develop and evaluate a novel ultrasound-activated peptide with enhanced antibacterial efficacy and reduced toxicity.
• To investigate the mechanism of action for ultrasound-mediated peptide activation and bacterial disruption.

Main Methods:

• Peptide library screening and selection based on piezoelectric diphenylalanine (FF) sequences, low toxicity, and positive charge.
• All-atom molecular dynamics simulations to elucidate peptide-membrane interactions and ultrasound effects.
• In vitro antibacterial assays against clinically relevant resistant bacterial strains.
• In vivo efficacy testing in a goat model of intervertebral infection.

Main Results:

• The selected peptide, FFRKSKEK, demonstrated >99% broad-spectrum antibacterial efficiency against methicillin-resistant bacteria within 15 minutes of ultrasound irradiation.
• Ultrasound was shown to enhance peptide membrane penetration and induce reactive oxygen species generation via piezoelectric polarization.
• The sonosensitive peptide exhibited negligible toxicity and low self-antibacterial activity.
• FFRKSKEK outperformed vancomycin in treating experimental intervertebral infections in a goat model.

Conclusions:

• Ultrasound-activated antimicrobial peptides represent a promising strategy for combating antibiotic-resistant infections.
• The FFRKSKEK peptide offers a potent, rapid, and targeted approach to antimicrobial therapy.
• This approach may provide a clinically relevant alternative to conventional antibiotics for difficult-to-treat infections.