Biophysical investigations into the interactions between antimicrobial peptides of the epithelial defense and microbial cell envelopes

上皮防御抗菌肽与微生物细胞包膜之间相互作用的生物物理学研究

• 批准号: 166433170
• 负责人: Professor Dr. Thomas Gutsmann
• 金额: --
• 依托单位: Forschungsgruppe Biophysik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2012-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/166433170?language=en
• 关键词: Biophysical; investigations; into; interactions; between

A prerequisite for antimicrobial peptides (AMPs) to kill bacteria is to destroy bacterial lipid membranes or to permeate them. We will investigate the interaction between AMPs of the epithelial defense system and natural or reconstituted lipid membranes. Recent results revealed different modes of action, which are highly peptide and lipid specific. We will concentrate on five topics within the context of peptide-lipid interactions: (1) Characterization of the molecular interaction mechanisms between certain natural AMPs and lipid membranes. (2) Synthesis of membrane-active peptides based on the natural AMPs. The goal is an increase of the antimicrobial activities, a reduction of cytotoxicity, and an increase of the neutralization of released bacterial virulence factors. (3) The possible induction of resistances of bacteria by the AMPs will be investigated in particular with respect to modifications of the lipid composition of the bacterial membranes. (4) In addition to the well established reconstitution models of the membranes of Gram-negative bacteria, respective reconstitution systems for the cell envelope of Gram-positive bacteria, archaea, and mycobacteria will be established. (5) Synergistic effects of membrane-active AMPs will be investigated in biological as well as in biophysical model systems.

抗菌肽（AMP）杀死细菌的先决条件是破坏细菌的脂质膜或渗透它们。我们将研究上皮防御系统的AMP与天然或重建的脂质膜之间的相互作用。最近的研究结果揭示了不同的作用模式，这是高度肽和脂质特异性。我们将集中在肽-脂质相互作用的背景下的五个主题：（1）某些天然AMP和脂质膜之间的分子相互作用机制的表征。(2)基于天然AMP的膜活性肽的合成。目标是增加抗微生物活性，降低细胞毒性，并增加释放的细菌毒力因子的中和作用。(3)将研究AMP对细菌抗性的可能诱导，特别是关于细菌膜的脂质组成的修饰。(4)除了已建立的革兰氏阴性菌膜的重建模型外，还将建立革兰氏阳性菌、古细菌和分枝杆菌细胞包膜的相应重建系统。(5)膜活性AMP的协同效应将在生物学以及生物物理模型系统中进行研究。