Pathogenesis to cooperation in the microbiome of a soil amoeba

描述(申请人提供)：真核生物不断地与大量不同的微生物相互作用。这些互动可能会以多方面的方式极大地影响双方的命运、演变和反应。了解细菌和真核生物之间的不同相互作用及其潜在机制，可以深入了解寄主抵抗策略、细菌发病机制和相互合作。有趣的是，与非载体克隆相比，社会变形虫的载体克隆已经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。盘状芽孢杆菌能适应多种生物技术，可被重要的人类病原体感染，并与多种微生物物种表现出不同和多样的相互作用。这些属性使其成为探测真核生物-细菌界面的强大系统。我的研究目的是定义盘状芽孢杆菌克隆与细菌物种之间的差异相互作用，并确定支持这些相互作用的基因和共同进化轨迹及其相关结果。我的具体目的是：1.确定携带者和非携带者盘基菌阿米巴克隆对细菌致病的差异反应。2.研究阿米巴-细菌共同进化对双方的影响。3.确定阿米巴-细菌界面的相关基因。通过这项工作，我将建立框架，以更好地定义这一模式系统，洞察真核生物-微生物合作发展和崩溃中的进化压力，并识别参与宿主-微生物互惠关系的基因。这一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，这些进化途径规定了感染和定居/合作之间的细微界限，以及不同宿主反应在这些事件中的作用。最后，这项工作将为更深入地分析阿米巴-细菌界面所涉及的分子机制铺平道路，从而能够更好地解决沿更广泛的共生连续体的跨王国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.