Molecular patterns for recognition and prey discrimination during phagocytic predation on fungi

真菌吞噬捕食过程中识别和猎物辨别的分子模式

• 批准号: 439291664
• 负责人: Professor Dr. Falk Hillmann
• 金额: --
• 依托单位: Bereich Maschinenbau/ Verfahrens- und Umwelttechnik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/439291664?language=en
• 关键词: Molecular; patterns; recognition; prey; discrimination

Fungi are major players in terrestrial ecosystems, with only some of them causing infections in higher organisms including humans. Mutual interactions with other microorganisms are among the key factors for their diversity, but are also increasingly recognized as a driving force for virulence. Among these, predation is known to cause substantial selective effects in higher organisms, summarized as the evolutionary arms race, but little is known how such relationships have shaped microbial communities. The Amoebozoa form a highly diverse group within the eukaryotic kingdom comprising mostly unicellular microorganism which all share a predatory lifestyle. Their undefined cell shape allows them to enclose and incorporate microbial cells by phagocytosis, a process that is also exploited by innate immune cells to eradicate invading bacteria and fungi. Despite their role as environmental predators and potential to study microbial phagocytosis, their complex biology has limited the number of model amoebae to a single one – Dictyostelium discoideum. Within this project we will exploit P. aurantium, a recently isolated fungivorous amoeba, to study the selective effects and molecular targets of phagocytic predation on fungal cells. A fully annotated genome and established protocols for large scale cultivations with different fungal prey species, including human pathogens, have made P. aurantium a suitable model to study fungal recognition and killing in a high throughput manner. Using a targeted approach to elucidate the role of essential cofactors, in combination with a large scale screening of defined mutant libraries, the project aims to identify single genes and metabolic pathways that have been under selective pressure by environmental phagocytes. As the process of phagocytosis is highly conserved from amoebozoa to innate immune cells, it is well conceivable that some of them will prove to be highly relevant during infection of higher hosts. The project is meant to open a rarely considered ecological and evolutionary perspective to fungal virulence and may also identify new targets for antifungal drugs and diagnostics.

真菌是陆地生态系统的主要参与者，其中只有一些会引起包括人类在内的高等生物的感染。与其他微生物的相互作用是其多样性的关键因素之一，但也越来越多地被认为是毒力的驱动力。其中，捕食已知会在高等生物中引起大量的选择性效应，概括为进化军备竞赛，但很少有人知道这种关系如何塑造微生物群落。阿米巴虫在真核生物界中形成了一个高度多样化的群体，主要由单细胞微生物组成，它们都有着掠夺性的生活方式。它们不确定的细胞形状使它们能够通过吞噬作用包围和合并微生物细胞，这一过程也被先天免疫细胞用来消灭入侵的细菌和真菌。尽管它们作为环境捕食者的作用和研究微生物吞噬作用的潜力，但它们复杂的生物学特性将模型变形虫的数量限制为单一的一种-盘基网柄变形虫。在这个项目中，我们将利用P. aurantium，一种最近分离的食真菌阿米巴，研究吞噬捕食对真菌细胞的选择性作用和分子靶点。完全注释的基因组和建立的大规模培养不同的真菌猎物物种，包括人类病原体的协议，使P. aurantium一个合适的模型，以研究真菌的识别和杀死在一个高通量的方式。该项目使用有针对性的方法来阐明必需辅助因子的作用，并结合对定义的突变体库的大规模筛选，旨在识别受到环境吞噬细胞选择压力的单个基因和代谢途径。由于从阿米巴原虫到先天免疫细胞的吞噬过程是高度保守的，因此可以想象，其中一些在感染高等宿主期间将被证明是高度相关的。该项目旨在为真菌毒力开辟一个很少考虑的生态和进化视角，也可能为抗真菌药物和诊断确定新的靶点。