Investigation of Francisella virulence and host cell defense mechanisms in Dictyostelium

盘基网柄菌弗朗西斯菌毒力和宿主细胞防御机制的研究

• 批准号: 261094593
• 负责人: Dr. Monica Hagedorn
• 金额: --
• 依托单位: HMU Research, Development und Innovation gGmbH (HMU RDI)
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/261094593?language=en
• 关键词: Investigation; Francisella; virulence; host; cell

The genus Francisella comprises intracellular pathogens that can cause potentially fatal infections in humans (tularemia caused by F. tularensis) and major economic losses, e.g. F. noatunensis in aquaculture. Because of the high virulence of F. tularensis and the lack of suitable model organisms their infection of phagocytic immune cells is not well understood. In the proposed project we want to establish the amoeba Dictyostelium as a host system to study Francisella virulence and cellular host defense mechanisms. Our preliminary experiments indicate that Dictyostelium is efficiently infected by F. noatunensis, a natural fish pathogen and genetically close to F. tularensis. The use of molecular, cell biological and microscopical approaches will allow us to dissect the pathway which leads to establishment and maintenance of infection. Furthermore, with the help of Francisella knock-out mutants we will be able to investigate the role of conserved virulence loci in infection (e.g. iglC).The new model system will allow the dissection of interactions between the phagocytic host cell and pathogenic Francisella in a genetically tractable system. It is a long-term goal to use this system for screening approaches that allow either the identification of host pathways, Francisella virulence factors or chemical compounds affecting Francisella growth in phagocytes.

弗朗西丝氏菌属包括可在人类中引起潜在致命感染的细胞内病原体（由F. tularensis）和重大经济损失，如F. noatunensis在水产养殖中的应用由于F.土拉热病和缺乏合适的模式生物，它们对吞噬免疫细胞的感染还没有很好的了解。本研究拟建立以网囊阿米巴为宿主的系统，研究弗朗西斯菌的毒力和宿主细胞防御机制。我们的初步实验表明，网囊藻能有效地被F. noatunensis是一种天然鱼类病原菌，与F.土拉热。使用分子，细胞生物学和显微镜的方法将使我们能够解剖的途径，导致建立和维持感染。此外，在Francisella敲除突变体的帮助下，我们将能够研究保守的毒力位点在感染中的作用（例如iglC）。新的模型系统将允许在遗传上易于处理的系统中解剖吞噬宿主细胞和致病Francisella之间的相互作用。这是一个长期的目标，使用该系统的筛选方法，允许识别宿主途径，弗朗西斯菌毒力因子或化学化合物影响弗朗西斯菌在吞噬细胞中的生长。