Hong Sungyoup, Takahashi Haruko, Nadres Enrico T, Mortazavian Hamid, Caputo Gregory A, Younger John G, Kuroda Kenichi
Department of Emergency Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, Michigan, United States of America.
PLoS One. 2017 Jan 6;12(1):e0169262. doi: 10.1371/journal.pone.0169262. eCollection 2017.
In this report, we demonstrate the pH-dependent, in vitro antimicrobial activity of a cationic, amphiphilic random copolymer against clinical isolates of drug-resistant Staphylococcus aureus. The polymer was developed toward a long-term goal of potential utility in the treatment of skin infections. The proposed mechanism of action of the polymer is through selectively binding to bacterial membranes and subsequent disruption of the membrane structure/integrity, ultimately resulting in bacterial cell death. The polymer showed bactericidal activity against clinical isolates of methicillin-resistant or vancomycin-intermediate S. aureus. The polymer was effective in killing S. aureus at neutral pH, but inactive under acidic conditions (pH 5.5). The polymer did not exhibit any significant hemolytic activity against human red blood cells or display cytotoxicity to human dermal fibroblasts over a range of pH values (5.5-7.4). These results indicate that the polymer activity was selective against bacteria over human cells. Using this polymer, we propose a new potential strategy for treatment of skin infections using the pH-sensitive antimicrobial polymer agent that would selectively target infections at pH-neutral wound sites, but not the acidic, healthy skin.
在本报告中，我们展示了一种阳离子两亲性无规共聚物对耐多药金黄色葡萄球菌临床分离株的pH依赖性体外抗菌活性。该聚合物是朝着在皮肤感染治疗中潜在应用的长期目标开发的。该聚合物拟议的作用机制是通过选择性地结合细菌膜并随后破坏膜结构/完整性，最终导致细菌细胞死亡。该聚合物对耐甲氧西林或万古霉素中介的金黄色葡萄球菌临床分离株表现出杀菌活性。该聚合物在中性pH值下能有效杀死金黄色葡萄球菌，但在酸性条件（pH 5.5）下无活性。在一系列pH值（5.5 - 7.4）范围内，该聚合物对人红细胞未表现出任何显著的溶血活性，对人皮肤成纤维细胞也未显示出细胞毒性。这些结果表明，该聚合物的活性对细菌具有选择性，而对人体细胞无选择性。使用这种聚合物，我们提出了一种治疗皮肤感染的新潜在策略，即使用对pH敏感的抗菌聚合物制剂，该制剂将选择性地靶向pH中性伤口部位的感染，而不是酸性的健康皮肤。
