A biomimetic peptide recognizes and traps bacteria in vivo as human defensin-6

Area of Science:

• Biomaterials Science
• Infectious Diseases
• Peptide Therapeutics

Background:

• Broad-spectrum antibiotics can lead to flora disequilibrium and drug resistance, posing significant health risks.
• There is a critical need for precise and effective antimicrobial agents to combat bacterial infections.

Purpose of the Study:

• To design and evaluate a human defensin-6 mimic peptide (HDMP) as a novel antimicrobial agent.
• To investigate the mechanism of action of HDMP in inhibiting bacterial invasion.
• To assess the in vivo efficacy of HDMP against bacterial infections.

Main Methods:

• Design of a human defensin-6 mimic peptide (HDMP) incorporating ligand and self-assembling sequences.
• Evaluation of HDMP's bacterial recognition via ligand-receptor interactions.
• Assessment of bacterial trapping through in situ adaptive self-assembly into nanofibrous networks.
• Testing HDMP efficacy in four distinct animal infection models, including methicillin-resistant Staphylococcus aureus (MRSA) bacteremia.

Main Results:

• HDMP effectively inhibited bacterial invasion in vivo by mimicking human defensin-6.
• The peptide recognized and trapped bacteria using ligand-receptor interactions and self-assembling nanofibrous networks.
• Infection rates were significantly decreased across four animal models.
• HDMP nanoparticles (5 mg/kg) achieved a 100% survival rate in mice with MRSA bacteremia, outperforming vancomycin (83.3% survival rate).

Conclusions:

• The designed biomimetic peptide (HDMP) acts as a precise and highly efficient antimicrobial agent.
• HDMP demonstrates significant potential for treating bacterial infections, including those caused by antibiotic-resistant strains.
• This approach offers a promising alternative to conventional antibiotic therapies.