Octenidine: Novel insights into the detailed killing mechanism of Gram-negative bacteria at a cellular and molecular level
Octenidine: Novel insights into the detailed killing mechanism of Gram-negative bacteria at a cellular and molecular level
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DOI：
10.1016/j.ijantimicag.2020.106146
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发表时间：
2020-11-01
影响因子：
10.8
通讯作者：
Lohner, Karl
中科院分区：
文献类型：
--
作者：
Malanovic, Nermina;On, Ayse;Lohner, Karl
奥替尼啶 (OCT) 是一种广泛使用的抗菌分子，其抗菌谱涵盖多种细菌和真菌。然而，详细的杀伤分子机制尚未阐明。我们研究的目的是使用大肠杆菌作为模型生物体以及相应的模型膜，研究 OCT 对革兰氏阴性菌的有效作用方式。通过电子显微镜观察 OCT 对细胞形态的影响，通过 zeta 电位、荧光显微镜和光谱学观察影响膜完整性（表面电荷、流动性、透化和去极化）的变化。使用差示扫描量热法、X 射线散射和荧光技术解决了 OCT 与膜磷脂的特定相互作用。 OCT 中和大肠杆菌的表面电荷，导致外膜破裂和细胞壁急剧损失，并进一步穿透周质空间到达内膜。模型膜显示 OCT 插入双层的疏水性脂肪酰基链区域，诱导完全脂质紊乱。膜完整性的丧失也反映在膜去极化和膜流动性的变化上，如电子显微镜所示。将 OCT 插入大肠杆菌的外膜和内膜会导致脂质排列混乱，从而导致细胞包膜快速破裂。我们认为，这种基于纯粹物理相互作用的非特异性作用模式是非常广泛的抗菌谱的基础，并且使得 OCT 不太可能产生耐药性。 (C) 2020 作者。由爱思唯尔有限公司出版
Octenidine (OCT) is a widely used antiseptic molecule with an antimicrobial spectrum covering a broad range of bacteria and fungi. However, the detailed molecular mechanism of killing has not yet been elucidated. The objective of our study was to investigate the mode of action of OCT's potent effect on Gram-negative bacteria using Escherichia coli as a model organism as well as corresponding model membranes. The effects of OCT on cellular morphology were observed by electron microscopy, changes affecting membrane integrity (surface charge, fluidity, permeabilisation and depolarisation) by zeta potential, fluorescence microscopy and spectroscopy. Specific interactions of OCT with membrane phospholipids were addressed using differential scanning calorimetry, X-ray scattering and fluorescence techniques. OCT neutralises the surface charge of E. coli leading to disruption of the outer membrane and dramatic loss of the cell wall and further penetrates through the periplasmic space reaching the inner membrane. Model membranes showed that OCT inserts into the hydrophobic fatty acyl chain region of the bilayer, inducing complete lipid disorder. The loss of membrane integrity is also reflected by membrane depolarisation and changes in membrane fluidity as shown by electron microscopy. Insertion of OCT into the outer and inner membrane of E. coli results in a chaotic lipid arrangement that leads to rapid disruption of the cell envelope. We propose that this unspecific mode of action based on purely physical interactions is the basis of the very broad antimicrobial profile and makes it unlikely that resistance to OCT will develop. (C) 2020 The Authors. Published by Elsevier Ltd.