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Construction, mechanism, and antibacterial resistance insight into polypeptide-based nanoparticles

机译：基于多肽的纳米粒子的构建，机制和抗菌性抗性

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摘要

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 mu g mL(-1) 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.
机译：抗药性细菌的出现对公共卫生构成了严重的威胁。传统的抗生素具有特异性细胞内靶点和通过化学方式消毒，这易于导致耐药性的发展，因此，由于其独特的性质，阳离子肽作为有前途的抗生素试剂引起了广泛的关注。在此，我们报告了一类具有伯氨基的两亲肽基果胶聚合物。通过扫描电子显微镜（SEM）和动态光散射（DLS）自发地自组装成带正电荷的纳米颗粒。生物学测定表明，纳米颗粒表现出对革兰氏阳性和革兰氏阴性细菌的广谱抗菌效果，其对六个临床细菌的16μg（-1）的MIC，即E. Faecalis，金黄色葡萄球菌， MRSA，VRE，P. Aruginosa和K.Pneumonia和三种细菌菌株大肠杆菌和大肠杆菌生产Ndm-1和IMIS，并在S. aureus和大肠杆菌上显示出95.6％和94.7％的灭菌率。 ， 分别。重要的是，纳米颗粒不会导致在14个通道后测试的正常和耐药细菌的耐药性，并在小鼠成纤维细胞上显示出低毒性（L929）。荧光染色，导电性，SEM和表面等离子体共振（SPR）表征表明，纳米颗粒最初与细菌表面结合，然后用它们的苯基刺穿细菌的膜，最后破坏了膜，产生的膜在离子泄漏并因此表现出广谱抗菌效果。这种纳米颗粒的这种杀菌机制不会导致易受发育耐药性的细菌。该研究提供了有望的抗菌材料的发展途径。

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  • 来源
    《Biomaterials Science》 |2019年第10期|共11页
  • 作者

    Zhen Jian-Bin; Zhao Mu-Han; Ge Ying; Liu Ya; Xu Li-Wei; Chen Cheng; Gong Yong-Kuan; Yang Ke-Wu;

  • 作者单位

    Northwest Univ Coll Chem &

    Mat Sci Chem Biol Innovat Lab Minist Educ Key Lab Synthet &

    Nat Funct Mol Chem 1 Xuefu Ave Xian 710127 Shaanxi Peoples R China;

    Northwest Univ Coll Chem &

    Mat Sci Chem Biol Innovat Lab Minist Educ Key Lab Synthet &

    Nat Funct Mol Chem 1 Xuefu Ave Xian 710127 Shaanxi Peoples R China;

    Northwest Univ Coll Chem &

    Mat Sci Chem Biol Innovat Lab Minist Educ Key Lab Synthet &

    Nat Funct Mol Chem 1 Xuefu Ave Xian 710127 Shaanxi Peoples R China;

    Northwest Univ Coll Chem &

    Mat Sci Chem Biol Innovat Lab Minist Educ Key Lab Synthet &

    Nat Funct Mol Chem 1 Xuefu Ave Xian 710127 Shaanxi Peoples R China;

    Northwest Univ Coll Chem &

    Mat Sci Chem Biol Innovat Lab Minist Educ Key Lab Synthet &

    Nat Funct Mol Chem 1 Xuefu Ave Xian 710127 Shaanxi Peoples R China;

    Northwest Univ Coll Chem &

    Mat Sci Chem Biol Innovat Lab Minist Educ Key Lab Synthet &

    Nat Funct Mol Chem 1 Xuefu Ave Xian 710127 Shaanxi Peoples R China;

    Northwest Univ Coll Chem &

    Mat Sci Chem Biol Innovat Lab Minist Educ Key Lab Synthet &

    Nat Funct Mol Chem 1 Xuefu Ave Xian 710127 Shaanxi Peoples R China;

    Northwest Univ Coll Chem &

    Mat Sci Chem Biol Innovat Lab Minist Educ Key Lab Synthet &

    Nat Funct Mol Chem 1 Xuefu Ave Xian 710127 Shaanxi Peoples R China;

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  • 正文语种 eng
  • 中图分类 分子生物学;
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