Self-assembly antimicrobial peptide for treatment of multidrug-resistant bacterial infection

Abstract

The wide-spreading of multidrug resistance poses a significant threat to human and animal health. Although antimicrobial peptides (AMPs) show great potential application, their instability has severely limited their clinical application. Here, self-assembled AMPs composed of multiple modules based on the principle of associating natural marine peptide N6 with ß-sheet-forming peptide were designed. It is noteworthy that one of the designed peptides, FFN could self-assemble into nanoparticles at 35.46 µM and achieve a dynamic transformation from nanoparticles to nanofibers in the presence of bacteria, resulting in a significant increase in stability in trypsin and tissues by 1.72–57.5 times compared to that of N6. Additionally, FFN exhibits a broad spectrum of antibacterial activity against multidrug-resistant (MDR) gram-positive (G + ) and gram-negative (G − ) bacteria with Minimum inhibitory concentrations (MICs) as low as 2 µM by membrane destruction and complemented by nanofiber capture. In vivo mouse mastitis infection model further confirmed the therapeutic potential and promising biosafety of the self-assembled peptide FFN, which can effectively alleviate mastitis caused by MDR Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus ), and eliminate pathogenic bacteria. In conclusion, the design of peptide-based nanomaterials presents a novel approach for the delivery and clinical translation of AMPs, promoting their application in medicine and animal husbandry. Graphical Abstract Supplementary Information The online version contains supplementary material available at 10.1186/s12951-024-02896-5.