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Bacterial membrane permeability of antimicrobial polymethacrylates: Evidence for a complex mechanism from super-resolution fluorescence imaging.
Acta Biomaterialia ( IF 9.4 ) Pub Date : 2020-03-14 , DOI: 10.1016/j.actbio.2020.03.011 Thomas D Michl 1 , Ben Hibbs 2 , Lauren Hyde 2 , Almar Postma 3 , Dung Thuy Thi Tran 1 , Aigerim Zhalgasbaikyzy 1 , Krasimir Vasilev 1 , Laurence Meagher 4 , Hans J Griesser 5 , Katherine E S Locock 6
Acta Biomaterialia ( IF 9.4 ) Pub Date : 2020-03-14 , DOI: 10.1016/j.actbio.2020.03.011 Thomas D Michl 1 , Ben Hibbs 2 , Lauren Hyde 2 , Almar Postma 3 , Dung Thuy Thi Tran 1 , Aigerim Zhalgasbaikyzy 1 , Krasimir Vasilev 1 , Laurence Meagher 4 , Hans J Griesser 5 , Katherine E S Locock 6
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Amphiphilic polymers bearing cationic moieties are an emerging alternative to traditional antibiotics given their broad-spectrum activity and low susceptibility to the development of resistance. To date, however, much remains unclear regarding their mechanism of action. Using functional assays (ATP leakage, cell viability, DNA binding) and super-high resolution structured illumination microscopy (OMX-SR) of fluorescently tagged polymers, we present evidence for a complex mechanism, involving membrane permeation as well as cellular uptake, interaction with intracellular targets and possible complexation with bacterial DNA. STATEMENT OF SIGNIFICANCE: This manuscript details the first study to systematically and directly investigate the mechanism of action of antimicrobial polymers, using super-resolution fluorescence imaging as well as functional assays. While many in the field cite membrane permeation as the sole mechanism underlying the activity of such polymers, we present evidence for multimodal actions including high cellular uptake and interaction with intracellular targets. It is also the first report to show competitive binding of antimicrobial polymers with bacterial DNA in a dose-dependent manner.
中文翻译：
抗菌聚甲基丙烯酸酯的细菌膜渗透性：来自超分辨率荧光成像的复杂机制的证据。
带有阳离子部分的两亲性聚合物由于其广谱活性和对耐药性发展的低敏感性而成为传统抗生素的新兴替代品。然而，迄今为止，关于它们的作用机理尚不清楚。使用功能性分析（ATP泄漏，细胞活力，DNA结合）和荧光标记聚合物的超高分辨率结构照明显微镜（OMX-SR），我们为复杂的机制提供了证据，涉及膜的渗透以及细胞的吸收，与细胞的相互作用。细胞内靶标以及可能与细菌DNA的复合。意义声明：该手稿详细介绍了首次进行系统且直接研究抗微生物聚合物作用机理的研究，使用超分辨率荧光成像以及功能测定。尽管该领域的许多人认为膜渗透是这种聚合物活性的唯一机制，但我们提供了多峰作用的证据，包括高细胞摄取和与细胞内靶标的相互作用。这也是第一个以剂量依赖性方式显示抗微生物聚合物与细菌DNA竞争结合的报告。
更新日期：2020-03-14
中文翻译：
抗菌聚甲基丙烯酸酯的细菌膜渗透性：来自超分辨率荧光成像的复杂机制的证据。
带有阳离子部分的两亲性聚合物由于其广谱活性和对耐药性发展的低敏感性而成为传统抗生素的新兴替代品。然而，迄今为止，关于它们的作用机理尚不清楚。使用功能性分析（ATP泄漏，细胞活力，DNA结合）和荧光标记聚合物的超高分辨率结构照明显微镜（OMX-SR），我们为复杂的机制提供了证据，涉及膜的渗透以及细胞的吸收，与细胞的相互作用。细胞内靶标以及可能与细菌DNA的复合。意义声明：该手稿详细介绍了首次进行系统且直接研究抗微生物聚合物作用机理的研究，使用超分辨率荧光成像以及功能测定。尽管该领域的许多人认为膜渗透是这种聚合物活性的唯一机制，但我们提供了多峰作用的证据，包括高细胞摄取和与细胞内靶标的相互作用。这也是第一个以剂量依赖性方式显示抗微生物聚合物与细菌DNA竞争结合的报告。
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