Identification of virulence determinants of the human-pathogenic fungus Aspergillus fumigatus by proteome analysis

通过蛋白质组分析鉴定人类致病真菌烟曲霉的毒力决定因素

• 批准号: 5426917
• 负责人: Professor Dr. Axel Brakhage, Ph.D.
• 金额: --
• 依托单位: Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. Hans-Knöll-Institut
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2004
• 资助国家: 德国
• 起止时间: 2003-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5426917?language=en
• 关键词: Identification; virulence; determinants; human; pathogenic

Aspergillus fumigatus has become the most important airborne fungal pathogen of humans causing pneumonia and invasive disseminated disease with high mortality in the immunocompromised host. Pathogenic fungi need to deal with a variety of environmental challenges during the course of an infection. The ability to meet these challenges requires the expression of many genes. To obtain a comprehensive overview about the proteins present during different infectious processes and potentially important for virulence, we have started to establish proteome analysis for A. fumigatus. Within this priority programme we aim at generating proteome data of A. fumigatus growing under different conditions including the cocultivation of the fungus with macrophages, neutrophils and the reisolation of the fungus from infected mice. Based on these data together with data from other groups, a proteome data base will be established. Interesting genes identified by proteome analysis will be analysed both genetically and biochemically. Deletion mutants of the respective genes will be tested in both macrophage assays and in a low dose, inhalative mouse infection model to determine the contribution of these genes to virulence. An immunogenic transgenic A. fumigatus strain will be generated to analyse the development of a specific immune reaction in living mice. These investigations will lead to the identification of regulatory circuits important for virulence, a better understanding of the communication between pathogen and host and eventually to the identification of targets for antifungal drugs.

曲霉菌已成为人类的最重要的空中真菌病原体，导致肺炎和侵袭性传播疾病，在免疫功能低下的宿主中死亡高死亡。致病真菌需要在感染过程中应对各种环境挑战。应对这些挑战的能力需要许多基因的表达。为了获得有关在不同感染过程中存在的蛋白质的全面概述，对毒力可能很重要，我们已经开始为烟曲霉建立蛋白质组分析。在此优先级计划中，我们旨在生成在不同条件下生长的烟曲霉的蛋白质组数据，包括真菌与巨噬细胞，中性粒细胞的共培养以及被感染小鼠的真菌再异化。基于这些数据以及其他组的数据，将建立蛋白质组数据库。通过蛋白质组分析鉴定的有趣基因将在遗传和生化上分析。各个基因的缺失突变体将在巨噬细胞测定和低剂量的吸入小鼠感染模型中进行测试，以确定这些基因对毒力的贡献。将生成免疫原性的转基因烟曲霉菌株，以分析活小鼠特定免疫反应的发展。这些研究将导致对毒力重要的调节回路的鉴定，更好地理解病原体与宿主之间的通信，并最终确定抗真菌药物的靶标。