Antibacterial Low Molecular Weight Cationic Polymers: Dissecting the Contribution of Hydrophobicity, Chain Length and Charge to Activity.
Antibacterial Low Molecular Weight Cationic Polymers: Dissecting the Contribution of Hydrophobicity, Chain Length and Charge to Activity.
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DOI：
10.1039/c5ra24361k
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发表时间：
2016-01-01
期刊：
影响因子：
3.9
通讯作者：
Whittaker MR
中科院分区：
文献类型：
--
作者：
Grace JL;Huang JX;Cheah SE;Truong NP;Cooper MA;Li J;Davis TP;Quinn JF;Velkov T;Whittaker MR
阳离子性和疏水性的平衡对抗菌聚合物的性能有着深远的影响。为此，通过Cu(0)介导聚合，使用三种不同的阳离子单体和两种引发剂，合成了24种具有独特低聚合度的阳离子聚合物库，并提供了两种不同的烃链尾长度（C2和C12）。当对几种细菌进行检测时，这些聚合物显示出结构依赖性的抗菌活性，即金黄色葡萄球菌ATCC 29213，肺炎克雷伯菌ATCC 13883，鲍曼不动杆菌ATCC 19606和铜绿假单胞菌ATCC 27853作为革兰氏阳性和革兰氏阴性ESKAPE病原体的代表性色系。鉴定出5种性能最好的聚合物，对耐多粘菌素鲍曼不动杆菌ATCC 19606R菌株进行进一步的检测。具有最低DP和C12疏水尾部的聚合物被证明对所研究的细菌组提供最广泛的抗菌活性，这可以通过较低的最低抑制浓度（mic）来证明。确定了最佳的聚合物组成，并通过膜透性试验研究了其对大肠杆菌的作用机理。膜破坏被认为是细菌杀死细胞最可能的机制。
The balance of cationicity and hydrophobicity can profoundly affect the performance of antimicrobial polymers. To this end a library of 24 cationic polymers with uniquely low degrees of polymerization was synthesized via Cu(0)-mediated polymerization, using three different cationic monomers and two initiators: providing two different hydrocarbon chain tail lengths (C2 and C12). The polymers exhibited structure-dependent antibacterial activity when tested against a selection of bacteria, viz, Staphylococcus aureus ATCC 29213, Klebsiella pneumoniae ATCC 13883, Acinetobacter baumannii ATCC 19606, and Pseudomonas aeruginosa ATCC 27853 as a representative palette of Gram-positive and Gram-negative ESKAPE pathogens. The five best-performing polymers were identified for additional testing against the polymyxin-resistant A. baumannii ATCC 19606R strain. Polymers having the lowest DP and a C12 hydrophobic tail were shown to provide the broadest antimicrobial activity against the bacteria panel studied as evidenced by lower minimum inhibitory concentrations (MICs). An optimal polymer composition was identified, and its mechanism of action investigated via membrane permeability testing against Escherichia coli. Membrane disruption was identified as the most probable mechanism for bacteria cell killing.