Structural and biophysical characterization of the interaction between intracellular pathogens and phagosome membranes

细胞内病原体与吞噬体膜之间相互作用的结构和生物物理特征

• 批准号: 198141395
• 负责人: Professor Dr. Thomas Gutsmann
• 金额: --
• 依托单位: Forschungsgruppe Bioanalytische Chemie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/198141395?language=en
• 关键词: Structural; biophysical; characterization; interaction; between

Bacteria can be ingested by professional phagocytes. Within the phagosome different mechanisms lead to a killing of the bacteria. However, some bacterial species are able to survive within the phagosome. The interaction between these intracellular bacteria and phagosome membranes is a key to understand how the pathogens survive in this niche. Besides proteins, lipids play an essential role in this process. However, up to now only limited data on the lipid composition and the physicochemical membrane properties are published. We want to characterize the lipidome of sub-cellular compartments and compare them depending on the absence or presence of bacteria which arrest phagosome maturation at a pre-phagolysosome stage. Based on these results, we will investigate the underlying molecular mechanisms of survival using biophysical approaches. For this, we will analyze purified phagosome membranes as well as reconstituted lipid membranes composed of well defined lipid compositions mimicking the phagosome membrane. In particular the interactions of the glycolipid trehalose-dimycolate (TDM) from Mycobacteria and of the virulence-associated protein A (VapA) from Rhodococcus equi will be characterized in detail using these systems.

细菌可以被专业的吞噬细胞吞噬。在吞噬体内部，不同的机制导致细菌被杀死。然而，一些细菌种类能够在吞噬体中生存。这些细胞内细菌和吞噬体膜之间的相互作用是了解病原体如何在这个生态位中生存的关键。除了蛋白质，脂质在这个过程中也起着重要的作用。然而，到目前为止，关于脂质组成和物理化学膜性质的数据有限。我们想表征亚细胞区室的脂质组，并根据在吞噬体前阶段阻止吞噬体成熟的细菌的存在或缺失来比较它们。基于这些结果，我们将使用生物物理方法研究生存的潜在分子机制。为此，我们将分析纯化的吞噬体膜以及由明确定义的脂质成分组成的重组脂质膜，这些脂质成分模仿吞噬体膜。特别是来自分枝杆菌的糖脂海藻糖-二mycolate （TDM）和来自马红球菌的毒力相关蛋白A （VapA）的相互作用将使用这些系统进行详细表征。