Design of High-Selectivity Co-Assembled Peptide Nanofibers against Bacterial Infection in Piglets

Antibiotic resistance is an escalating global health concern that could result in tens of millions of deaths annually from drug-resistant bacterial infections in the future, especially in animal husbandry. Peptide antibacterial nanomaterials offer a competitive alternative to antibiotics because of their distinct mechanism of physically penetrating pathogenic biological membranes. This study developed amphiphilic co-assembled peptide nanofibers with high biological selectivity (PCBP-NCAP NFs) to overcome the high cytotoxicity of peptide PCBP and the low antibacterial activity of peptide NCAP. PCBP-NCAP NFs exhibit broad-spectrum antibacterial activity and excellent biocompatibility, with negligible in vivo and in vitro toxicity. Additionally, PCBP-NCAP NFs possess direct antibacterial efficacy and potential immunomodulatory capabilities using a piglet systemic infection model. Its unique mechanism of membrane penetration and the ability to bind to anionic components on the surface of pathogenic bacteria make them less susceptible to drug resistance. In conclusion, these findings have significant implications for the advancement of supramolecular peptide nanomedicines for clinical application and animal husbandry.