Membrane activity of the pentaene macrolide didehydroroflamycoin in model lipid bilayers
Membrane activity of the pentaene macrolide didehydroroflamycoin in model lipid bilayers
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DOI：
10.1016/j.bbamem.2014.10.038
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发表时间：
2015-02-01
影响因子：
3.4
通讯作者：
Hof, Martin
中科院分区：
文献类型：
--
作者：
Koukalova, Alena;Pokorna, Sarka;Hof, Martin
二脱氢flamycoin （DDHR）是最近分离到的多烯大环内酯家族成员，具有抗菌和抗真菌活性。然而，其作用机制尚未被研究。这个家族的抗生素是两亲性的；因此，它们具有膜活性，其生物作用局限于膜内，膜的组成和物理性质有利于靶生物对特定化合物的识别。在这项工作中，我们使用由巨大单层囊泡（GUVs）组成的模型脂质膜系统地研究了DDHR的作用。与此同时，使用家族的其他成员filipin III和amphotericin B进行了实验，并在这两种被大量研究的化合物的背景下描述了DDHR观察到的行为。研究表明，DDHR通过两种不同的机制破坏细胞膜，而这些机制的参与取决于胆固醇的存在。在guv中进行的泄漏试验和使用黑脂膜（BLM）进行的电导测量表明，在没有胆固醇的情况下形成的孔隙是短暂的，其大小取决于DDHR浓度。相反，胆固醇促进更明确的结构的形成，这些结构是暂时稳定的。(C) 2014 Elsevier B.V.版权所有
Didehydroroflamycoin (DDHR), a recently isolated member of the polyene macrolide family, was shown to have antibacterial and antifungal activity. However, its mechanism of action has not been investigated. Antibiotics from this family are amphiphilic; thus, they have membrane activity, their biological action is localized in the membrane, and the membrane composition and physical properties facilitate the recognition of a particular compound by the target organism. In this work, we use model lipid membranes comprised of giant unilamellar vesicles (GUVs) for a systematic study of the action of DDHR. In parallel, experiments are conducted using filipin III and amphotericin B, other members of the family, and the behavior observed for DDHR is described in the context of that of these two heavily studied compounds. The study shows that DDHR disrupts membranes via two different mechanisms and that the involvement of these mechanisms depends on the presence of cholesterol. The leakage assays performed in GUVs and the conductance measurements using black lipid membranes (BLM) reveal that the pores that develop in the absence of cholesterol are transient and their size is dependent on the DDHR concentration. In contrast, cholesterol promotes the formation of more defined structures that are temporally stable. (C) 2014 Elsevier B.V. All rights reserved.