Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, Chemical Biology Innovation Laboratory, College of Chemistry and Materials Science, Northwest University, 1 Xuefu Avenue, Xi'an 710127, P. R. China.
Biomater Sci. 2019 Oct 1;7(10):4142-4152. doi: 10.1039/c9bm01050e. Epub 2019 Jul 31.
The emergence of drug-resistant bacteria poses a serious threat to public health. The traditional antibiotics have specific intracellular targets and disinfect via chemical ways, which easily lead to the development of drug resistance, therefore, cationic peptides as promising antibiotic agents have attracted extensive attention due to their unique properties. Herein, we report a class of amphiphilic peptide-based pectinate polymers with primary amino groups. The polymers spontaneously self-assembled into the positively charged nanoparticles, which were evaluated and confirmed by scanning electron microscopy (SEM) and dynamic light scattering (DLS). Biological assays revealed that the nanoparticles showed broad-spectrum antibacterial efficacy against both Gram-positive and Gram-negative bacteria, exhibiting a MIC of 16 μg mL against six clinical bacteria, namely, E. faecalis, S. aureus, MRSA, VRE, P. aeruginosa, and K. pneumonia, and three bacterial strains E. coli and E. coli producing NDM-1 and ImiS, and showed a sterilization rate of 95.6% and 94.7% on S. aureus and E. coli, respectively. Importantly, the nanoparticles did not result in drug-resistance for both the normal and drug-resistant bacteria tested after 14 passages and showed low toxicity on the mouse fibroblast cells (L929). The fluorescence staining, electrical conductivity, SEM, and surface plasmon resonance (SPR) characterization suggested that the nanoparticles initially bound to the surface of the bacteria, then pierced into the membranes of the bacteria with their phenyl groups, and finally disrupted the membranes, resulting in ions leaking out and thus exhibiting broad-spectrum antibacterial efficacy. This bactericidal mechanism that the nanoparticles employed does not lead the bacteria susceptible to developing drug resistance. This study provides a promising pathway for the development of the efficient antibacterial materials.
耐药菌的出现对公共健康构成了严重威胁。传统抗生素具有特定的细胞内靶点，并通过化学方式进行消毒，这容易导致耐药性的产生。因此，阳离子肽作为有前途的抗生素引起了广泛关注，因为它们具有独特的性质。在本文中，我们报告了一类具有伯氨基的两亲性肽基果胶聚合物。聚合物自发自组装成带正电荷的纳米颗粒，通过扫描电子显微镜（SEM）和动态光散射（DLS）进行评估和确认。生物测定表明，纳米颗粒对革兰氏阳性和革兰氏阴性细菌均表现出广谱的抗菌功效，对六种临床分离菌（粪肠球菌、金黄色葡萄球菌、耐甲氧西林金黄色葡萄球菌、万古霉素耐药肠球菌、铜绿假单胞菌和肺炎克雷伯菌）的 MIC 为 16 μg mL，对三种产 NDM-1 和 ImiS 的大肠杆菌和大肠杆菌菌株的 MIC 为 16 μg mL，对金黄色葡萄球菌和大肠杆菌的杀菌率分别为 95.6%和 94.7%。重要的是，在 14 次传代后，纳米颗粒对测试的正常和耐药细菌均未导致耐药性，并对小鼠成纤维细胞（L929）表现出低毒性。荧光染色、电导率、SEM 和表面等离子体共振（SPR）特性表明，纳米颗粒最初与细菌表面结合，然后用其苯环基团刺穿细菌的细胞膜，最后破坏细胞膜，导致离子泄漏，从而表现出广谱的抗菌功效。纳米颗粒采用的这种杀菌机制不会使细菌容易产生耐药性。这项研究为开发高效抗菌材料提供了有前途的途径。
