Bacterial membranes represent an attractive target for the design of new antibiotics to combat widespread bacterial resistance to traditional inhibitor-based antibiotics. Understanding how antimicrobial peptides (AMPs) and other membrane-active agents attack membranes could facilitate the design of new, effective antimicrobials. AMPs, which are small, gene-encoded host defense proteins, offer a promising basis for the study of membrane-active antimicrobial agents. These peptides are cationic and amphipathic, spontaneously binding to bacterial membranes and inducing transmembrane permeability to small molecules. Yet there are often confusions surrounding the details of the molecular mechanisms of AMPs. Following the doctrine of structure–function relationship, AMPs are often viewed as the molecular scaffolding of pores in membranes. Instead we believe that the full mechanism of AMPs is understandable if we consider the interactions of AMPs with the whole membrane domain, where interactions induce structural transformations of the entire membrane, rather than forming localized molecular structures. We believe that it is necessary to consider the entire soft matter peptide-membrane system as it evolves through several distinct states. Accordingly, we have developed experimental techniques to investigate the state and structure of the membrane as a function of the bound peptide to lipid ratio, exactly as AMPs in solution progressively bind to the membrane and induce structural changes to the entire system. The results from these studies suggest that global interactions of AMPs with the membrane domain are of fundamental importance to understanding the antimicrobial mechanisms of AMPs.

中文翻译：

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了解膜活性抗菌肽

细菌膜是设计新抗生素以对抗细菌对传统抑制剂类抗生素的广泛耐药性的一个有吸引力的目标。了解抗菌肽 (AMP) 和其他膜活性剂如何攻击膜有助于设计新的有效抗菌剂。AMP 是一种小型的基因编码宿主防御蛋白，为研究膜活性抗菌剂提供了有希望的基础。这些肽是阳离子和两亲性的，自发地结合细菌膜并诱导小分子的跨膜渗透性。然而，围绕 AMP 分子机制的细节经常存在混淆。遵循结构-功能关系学说，AMPs 通常被视为膜中孔的分子支架。相反，如果我们考虑 AMP 与整个膜域的相互作用，我们认为 AMP 的完整机制是可以理解的，其中相互作用诱导整个膜的结构转变，而不是形成局部分子结构。我们认为有必要考虑整个软物质肽膜系统，因为它会通过几个不同的状态演变。因此，我们开发了实验技术来研究膜的状态和结构作为结合肽与脂质比率的函数，就像溶液中的 AMP 逐渐与膜结合并诱导整个系统的结构变化一样。