Pathogenesis to cooperation in the microbiome of a soil amoeba

描述（由申请人提供）：真核生物不断与大量不同的微生物相互作用。这些互动会以多方面的方式极大地影响伴侣双方的命运、进化和反应。了解细菌与真核生物之间的多种相互作用及其潜在机制，可以深入了解宿主的抗性策略、细菌的发病机制和相互合作。有趣的是，社会变形虫盘基骨虫的载体克隆与非载体克隆相比，已被证明含有多种细菌。在宿主体内，这些细菌提供食物和防御。在非载体克隆中，这些细菌是致病的。盘状棘球蚴可适应多种生物技术，可被重要的人类病原体感染，并与多种微生物物种表现出独特而多样的相互作用。这些特性使它成为探测真核-细菌界面的强大系统。我的研究目的是定义盘状盘孢菌克隆与细菌物种之间的差异相互作用，并确定这些相互作用及其相关结果的基因和共同进化轨迹。我的具体目标是：1。确定带菌者和非带菌者盘状盘基骨虫阿米巴克隆对细菌致病机制的不同反应。2. 检查变形虫-细菌共同进化对双方的影响。3. 鉴定与变形虫-细菌界面有关的基因。通过这项工作，我将建立一个框架来更好地定义这个模型系统，深入了解真核生物-微生物合作发展和破裂的进化压力，并确定参与宿主-微生物共生的基因。这个灵活的系统可以进一步应用于完善我们对进化途径的理解，这些途径指定了感染和定植/合作之间的细线，以及这些事件中不同宿主反应的作用。最后，这项工作将为更深入地分析涉及阿米巴-细菌界面的分子机制铺平道路，从而允许在更广泛的共生连续体中更大程度地解决跨界相互作用的动态原因和后果。

DESCRIPTION (provided by applicant): Eukaryotes constantly interact with an abundant array of different microbes. These interactions can drastically impact the fate, evolution, and responses of both partners in multifaceted ways. Understanding the diverse interactions between bacteria and eukaryotes and their underlying mechanisms can provide insight into host resistance strategies, bacterial pathogenesis, and mutual cooperation. Interestingly, carrier clones of the social amoeba Dictyostelium discoideum have been shown to harbor a variety of bacteria, in contrast to their non-carrier counterparts. In the host, these bacteria provide food and defense. In non-carrier clones, these bacteria are pathogenic. D. discoideum is amenable to a variety of biological techniques, can be infected by important human pathogens, and displays distinct and diverse interactions with a variety of microbial species. These attributes make it a powerful system for probing the eukaryote-bacteria interface. The purpose of my research is to define the differential interactions between D. discoideum clones with bacterial species, and to identify the genes and co-evolutionary trajectories underlying these interactions and their associated outcomes. My specific aims are to: 1. Determine the differential responses of carrier and non-carrier Dictyostelium discoideum amoeba clones to bacterial pathogenesis. 2. Examine the impact of amoeba- bacteria co-evolution on both partners. 3. Identify genes involved in the amoeba- bacteria interface. Through this work I will set up the framework to better define this model system, gain insight into evolutionary pressures in the development and breakdown of eukaryote-microbe cooperation, and identify genes involved in host-microbe mutualism. This flexible system can be further applied to refine our understanding of the evolutionary pathways that specify the fine line between infection and colonization/cooperation and the role of differential host-responses in these events. Finally, this work will pave the way for more in-depth analysis of the molecular mechanisms involved in the amoeba-bacterial interface, thereby allowing for greater resolution of the dynamic causes and consequences of trans- kingdom interactions along the wider symbiosis continuum.