Enhancement of Cationic Antimicrobial Materials via Cholesterol Incorporation
Enhancement of Cationic Antimicrobial Materials via Cholesterol Incorporation
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DOI：
10.1002/adhm.201300554
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发表时间：
2014-06-01
影响因子：
10
通讯作者：
Hedrick, James L.
中科院分区：
文献类型：
--
作者：
Coady, Daniel J.;Ong, Zhan Yuin;Hedrick, James L.
阳离子抗菌材料是治疗耐药细菌的有吸引力的选择。它们的膜溶解机制可以提供广谱抗微生物活性，同时在很大程度上否定天然抗性的发展。选择性是使用非特异性静电相互作用实现的，因为微生物膜比真核生物双层显示出显著更多的外围负电荷。膜结合后，结构发生变化，引起双层不稳定和细胞裂解。在此，增强膜同化的抗菌效果进行检查。胆固醇是一种在细胞膜内大量同化的可官能化的小分子，其被选择用于增加膜渗透能力以改善抗微生物活性。此外，胆固醇具有模板感兴趣的纳米结构的能力，由于其倾向于旋转面对面堆叠。利用有机催化开环聚合反应，从三种不同的胆甾醇基引发剂中合成了具有不同链长的阳离子聚碳酸酯。将胆固醇低聚物引入水性介质中产生具有高外部阳离子电荷密度的“硬币”形自组装体。对这些组装物的持续评价证明了对S. epidermidis、S.金黄色葡萄球菌E. coli、P. aeraginosa和C.白色念珠菌另外的结果表明，尽管重复亚致死剂量，E。大肠杆菌不会产生耐药性，并保持野生型最低抑菌浓度为31.3 mg L-1。
Cationic antimicrobial materials are an attractive option for treating drug-resistant bacteria. Their membrane lytic mechanism can provide broad spectrum antimicrobial activity while largely negating natural resistance development. Selectivity is achieved using non-specific electrostatic interactions since microbial membranes display significantly more peripheral negative charge than due eukaryotic bilayers. Following membrane association, structural changes occur causing bilayer destabilization and cell lysis. Herein, antimicrobial effects of enhanced membrane assimilation are examined. Cholesterol, a functionalizable small molecule that assimilates abundantly within cell membranes, is chosen to increase membrane penetration ability to improve antimicrobial activity. Furthermore, cholesterol has an ability to template interesting nanostructures due to its propensity for rotative face-on-face stacking. The installation of cationic polycarbonates with systematically varied chain lengths from three separate cholesteryl initiators is accomplished using organocatalytic ring-opening polymerization. Introduction of cholesteryl oligomers into aqueous media creates "coin" shaped self-assemblies possessing high exterior cationic charge density. Continued evaluation of these assemblies demonstrates broad spectrum activity against S. epidermidis, S. aureus, E. coli, P. aeraginosa, and C. albicans. Additional results show that, despite repeated sub-lethal dosing, E. coli does not evolve drug-resistance and maintains the wild-type minimum inhibitory concentration of 31.3 mg L-1.