Innovative Team of Antimicrobial Peptides and Alternatives to Antibiotics, Gene Engineering Laboratory, Feed Research Institute, Chinese Academy of Agricultural Sciences, 12 Zhongguancun Nandajie St., Haidian District, Beijing, 100081, China.
State Key Laboratory of Farm Animal Biotech Breeding, College of Biology Sciences, China Agricultural University, Beijing, 100193, China.
J Nanobiotechnology. 2024 Oct 30;22(1):668. doi: 10.1186/s12951-024-02896-5.
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.
多药耐药性的广泛传播对人类和动物健康构成了重大威胁。尽管抗菌肽（AMPs）具有很大的应用潜力，但它们的不稳定性严重限制了它们的临床应用。在这里，根据与天然海洋肽 N6 结合的原则，设计了由多个模块组成的自组装 AMPs。值得注意的是，设计的肽之一 FFN 可以在 35.46µM 下自组装成纳米颗粒，并在存在细菌的情况下从纳米颗粒动态转化为纳米纤维，与 N6 相比，在胰蛋白酶和组织中的稳定性提高了 1.72-57.5 倍。此外，FFN 通过破坏细胞膜并辅以纳米纤维捕获，对多药耐药（MDR）革兰氏阳性（G）和革兰氏阴性（G）细菌具有广谱的抗菌活性，最低抑菌浓度（MIC）低至 2µM。体内小鼠乳腺炎感染模型进一步证实了自组装肽 FFN 的治疗潜力和良好的生物安全性，它可以有效缓解由 MDR 大肠杆菌（E. coli）和金黄色葡萄球菌（S. aureus）引起的乳腺炎，并消除病原菌。总之，基于肽的纳米材料的设计为 AMPs 的传递和临床转化提供了一种新方法，促进了它们在医学和畜牧业中的应用。
