AfuInf - Proteome and polysaccharidome of Aspergillus fumigatus at early stage of infection

AfuInf - 感染早期烟曲霉的蛋白质组和多糖组

基本信息

批准号：
316898429
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：
Research Grants
财政年份：
2016
资助国家：
德国
起止时间：
2015-12-31 至 2020-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/316898429?language=en
关键词：
AfuInf Proteome polysaccharidome Aspergillus fumigatus

项目摘要

Although they do not convey the attribute epidemics, fungal infections are an increasingly significant medical problem. Humans contract fungal diseases that cause severe damage or kill at least as many people as tuberculosis or malaria. Among them, Aspergillus fumigatus is the most important airborne fungal mould that is responsible for diseases in immunocompetent as well as immunocompromised hosts with unacceptably high mortality rates in the latter cohort. The threat posed by A. fumigatus to hospital patients is attributable to a very poor understanding of the pathobiology of aspergillosis. Therefore, the major objective of this research program will be to investigate the spore (conidium), which is the infectious morphotype. A special focus will be on the cell wall of the resting and germinating conidium since we have identified several molecules of the cell wall, which are essential either for fungal virulence by modulating the host immune system but also for resistance against external insults. Until today, however, there is no comprehensive biochemical and genetic analysis of conidia, which is urgently required to understand the early stages of A. fumigatus infection. To address this fundamental problem, we have defined 3 tasks:In task 1, the landscape of the cell wall components of the dormant conidium and their structural organization will be deciphered by proteome and polysaccharidome analyses as well as structural studies. In task 2, the cell wall modifications and newly secreted proteins occurring during the early stages of germination will be identified. In task 3, the effect of cell wall-associated components from resting and germinating conidia on macrophages including the analysis of the phagolysosomal proteome will be deciphered and virulence of the respective mutants will be evaluated in a mouse infection model.The consortium is composed of the Aspergillus unit of the Institut Pasteur (head: J.-P. Latgé) and the Department of Microbiology and Molecular Biology, University of Jena and the Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (head: A. Brakhage). Since many years, these partners have been having an intense and fruitful collaboration on the study of A. fumigatus and have complementary expertise in, e.g., biochemistry, glycobiology, proteomics, bioinformatics, genetics and infection biology, all technologies required to work together to tackle the planned tasks.Our project addresses the important unanswered question: How can an airborne fungus become a human pathogen? Characterizing the infectious propagules in their dormant and early germinating stage is a key for the understanding of the establishment of the disease and the development of new prophylactic and antifungal therapies. Results obtained during this project with A. fumigatus can be expected to be of great benefit for the whole scientific field of fungal pathogenicity.

尽管它们没有传达属性发作，但真菌感染是越来越重大的医学问题。人类患有引起严重损害或至少与结核病或疟疾一样数量的真菌疾病。其中，曲霉菌是最重要的空中真菌霉菌，是导致免疫能力和免疫性疾病的疾病，后者同类中死亡率高可高。 A. fumigatus对医院患者所说的威胁归因于对曲霉病的病理生物学的不良理解。因此，该研究计划的主要目的是研究酱汁（分生孢子），即传染性形态。由于我们已经确定了细胞壁的几个分子，因此将特别关注静止和发芽分生孢子的细胞壁，这对于通过调节宿主免疫系统而对真菌病毒来说至关重要，并且对于抵抗外部侮辱性是必不可少的。但是，直到今天，尚无对分生孢子的全面生化和遗传分析，这迫切需要了解烟曲霉感染的早期阶段。为了解决这一基本问题，我们定义了3个任务：在任务1中，休眠分生圈的细胞壁成分及其结构组织的景观将由蛋白质组和多糖元分析以及结构研究决定。在任务2中，将确定细胞壁修饰和新分泌的蛋白质发生在发芽的早期阶段。在任务3中，将确定与细胞壁相关的成分对静止和发芽的分生孢子对巨噬细胞的影响，包括分析吞噬物质蛋白质组的分析，并将在小鼠感染模型中评估各自突变体的病毒。耶那（Jena）以及莱布尼兹自然产品研究与感染生物学研究所分子与应用微生物学系（头：A。Brakhage）。自多年以来，这些伴侣就在烟曲霉的研究上进行了激烈而富有成果的合作，并具有互补的专业知识，例如，生物化学，糖化学，蛋白质组学，蛋白质组学，生物信息学，遗传学和感染生物学，都需要解决计划的问题。在休眠和早期发芽阶段表征感染性繁殖体是理解疾病的建立以及新的抗真菌和抗真菌疗法的发展的关键。可以预期，该项目在该项目中获得的结果对真菌致病性的整个科学领域具有很大的好处。