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Combating Antibiotic-Resistant Bacterial Infection Using Coassembled Dimeric Antimicrobial Peptide-Based Nanofibers
Guoyu Li1, Haoran Deng1, Wanying Xu1
1College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, P. R. China.
Abstract:
The emergence of multidrug-resistant (MDR) pathogens, coupled with the limited effectiveness of existing antibiotics in eradicating biofilms, presents a significant threat to global health care. This critical situation underscores the urgent need for the discovery and development of antimicrobial agents. Recently, peptide-derived antimicrobial nanomaterials have shown promise in combating such infections. Amino acid noncovalent forces, notably π-π stacking and electrostatic interactions, remain underutilized for guiding the coassembly of peptides into bacteriostatic nanomaterials. Thus, we constructed a dimeric nanopeptide system using the disulfide bonds of cysteine. The self-assembly of dimeric peptides into nanofibers was realized by the interaction of π-π aromatic amino acids (Trp, Phe, and Pyr) and the electrostatic attraction between oppositely charged amino acids (Asp and Arg). The optimal dimeric peptide 2D2W exhibits potent antibacterial activity against resistant bacteria and is nontoxic. Mechanistically, 2D2W penetrated the outer membrane after electrostatic adsorption, resulting in plasma membrane depolarization, homeostatic disruption, and ultimately bacterial death. In a mouse model of peritonitis, 2D2W demonstrated efficacy in the in vivo treatment of bacterial infections. In conclusion, the design of dimeric nanopeptides co-driven by intermolecular forces provides a promising avenue for the development of high-performance antimicrobial nanomaterials. These advances may also facilitate the application and advancement of peptide-based bacteriostatic agents in clinical practice.
Insights
New dimeric nanopeptides, guided by amino acid interactions, show potent antibacterial activity against drug-resistant pathogens and biofilms. This breakthrough offers a promising strategy for developing novel antimicrobial nanomaterials for clinical use.
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.
