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.

中文翻译：

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亲水性噬菌体模拟膜活性抗菌剂揭示了纳米结构依赖的活性和选择性。

开发膜活性抗微生物剂（MAA）的普遍智慧是寻求微妙但尚未量化的阳离子-疏水性平衡。受噬菌体的启发，噬菌体使用纳米结构的蛋白质装置有效地，选择性地入侵细菌，在这里，我们通过设计模仿噬菌体的两个基本结构图案的球形和杆状聚合物分子刷（PMB）来研究纳米结构的抗生素作用。具有不同定义良好几何形状的三个模型PMB，由密集填充的聚（4-乙烯基-N）的多个相同副本组成-甲基吡啶碘化物）分支是通过受控/“活性”聚合合成的，让人联想到由蛋白质亚基的多个拷贝组成的病毒结构基序。我们显示，虽然组成PMB的单个线性链聚合物分支是亲水性的且抗微生物性较弱，但是一旦纳米结构发挥作用，两亲性就不是必需的抗生素性状。纳米结构的PMB诱导细菌的异常拓扑转变，但不会诱导哺乳动物膜形成孔。纳米结构的大小和形状进一步有助于确定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，低毒性和靶标特异性的MAA中的重要性。