Hydrophilic Phage-Mimicking Membrane Active Antimicrobials Reveal Nanostructure-Dependent Activity and Selectivity
Hydrophilic Phage-Mimicking Membrane Active Antimicrobials Reveal Nanostructure-Dependent Activity and Selectivity
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DOI：
10.1021/acsinfecdis.7b00076
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发表时间：
2017-09-01
影响因子：
5.3
通讯作者：
Liang, Hongjun
中科院分区：
文献类型：
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作者：
Jiang, Yunjiang;Zheng, Wan;Liang, Hongjun
开发膜活性抗菌剂（MAA）的普遍智慧是寻求微妙的，但无法量化的阳离子疏水平衡。受使用纳米结构蛋白质设备有效和选择性地入侵细菌的细菌的启发，我们在这里通过设计模拟噬菌体的两个基本结构基序的球形和棒状聚合物分子刷（PMB）来研究纳米结构的抗生素作用。三个模型PMB与不同的定义明确的几何形状组成的多个，相同的副本密集包装的聚（4-乙烯基-N-甲基吡啶碘）分支合成的控制/“活”聚合，让人想起的病毒结构基序组成的多个拷贝的蛋白质亚基。我们发现，虽然构成PMB的单个线性链聚合物分支是亲水性的，并且是弱抗菌性的，但是一旦纳米结构发挥作用，两亲性不是必需的抗生素特性。纳米结构的PMB诱导细菌而不是哺乳动物膜的不寻常的拓扑结构转变以形成孔。纳米结构的大小和形状进一步帮助定义PMB对不同细菌家族的抗生素活性和选择性。这项研究强调了纳米结构在设计具有高活性，低毒性和靶向特异性的MAA中的重要性。
The prevalent wisdom on developing membrane active antimicrobials (MAAs) is to seek a delicate, yet unquantified, cationic hydrophobic balance. Inspired by phages that use nanostructured protein devices to invade bacteria efficiently and selectively, we study here the antibiotic role of nanostructures by designing spherical and rod-like polymer molecular brushes (PMBs) that mimic the two basic structural motifs of bacteriophages. Three model PMBs with different well-defined geometries consisting of multiple, identical copies of densely packed poly(4-vinyl-N-methylpyridine iodide) branches are synthesized by controlled/"living" polymerization, reminiscent of the viral structural motifs comprised of multiple copies of protein subunits. We show that, while the individual linear-chain polymer branch that makes up the PMBs is hydrophilic and a weak antimicrobial, amphiphilicity is not a required antibiotic trait once nanostructures come into play. The nanostructured PMBs induce an unusual topological transition of bacterial but not mammalian membranes to form pores. The sizes and shapes of the nanostructures further help define the antibiotic activity and selectivity of the PMBs against different families of bacteria. This study highlights the importance of nanostructures in the design of MAAs with high activity, low toxicity, and target specificity.