Combating Antibiotic-Resistant Bacterial Infection Using Coassembled Dimeric Antimicrobial Peptide-Based Nanofibers.

Area of Science:

• Biomaterials Science
• Nanotechnology
• Infectious Diseases

Background:

• Multidrug-resistant (MDR) pathogens and antibiotic-resistant biofilms pose a severe global health threat.
• Existing antibiotics have limited efficacy against biofilms, necessitating novel antimicrobial agents.
• Peptide-derived antimicrobial nanomaterials show promise but require optimized assembly strategies.

Purpose of the Study:

• To develop a novel dimeric nanopeptide system for antimicrobial applications.
• To investigate the role of amino acid noncovalent forces in guiding peptide self-assembly.
• To evaluate the antibacterial efficacy and safety of the developed nanopeptide.

Main Methods:

• Construction of a dimeric nanopeptide system using cysteine disulfide bonds.
• Utilizing π-π stacking and electrostatic interactions for peptide self-assembly into nanofibers.
• Assessing antibacterial activity against resistant bacteria and in vitro/in vivo models.
• Investigating the mechanism of bacterial membrane disruption.

Main Results:

• The optimal dimeric peptide, 2D2W, demonstrated potent antibacterial activity against resistant bacteria.
• 2D2W exhibited low toxicity, indicating a favorable safety profile.
• Mechanistic studies revealed 2D2W disrupts bacterial homeostasis, leading to cell death.
• Effective in vivo treatment of bacterial peritonitis in a mouse model was observed.

Conclusions:

• Dimeric nanopeptides co-driven by intermolecular forces represent a promising platform for high-performance antimicrobial nanomaterials.
• This approach facilitates the development of effective peptide-based bacteriostatic agents for clinical applications.
• Optimized peptide self-assembly through noncovalent forces is key to combating MDR pathogens and biofilms.