Pathogenesis to cooperation in the microbiome of a soil amoeba

土壤阿米巴微生物组合作的发病机制

• 批准号: 8701889
• 负责人: Susanne DiSalvo
• 金额: $ 5.51万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8701889
• 关键词: Address; Amoeba genus; Animal Model; Bacteria; Bacterial Genes; Biochemical; Biological; Biological Models; Cells; Complex; Development; Dictyostelium discoideum; Eukaryota; Event; Evolution; Food Supply; Future; Genes; Genetic; Genomics; Host resistance; Human; Immune response; Infection; Light; Maintenance; Microbe; Modeling; Molecular; Molecular Analysis; Mus; Mutagenesis; Natural Selections; Organism; Outcome; Pathogenesis; Pathogenicity; Pathway interactions; Pattern; Research; Resistance; Resolution; Role; Soil; Specific qualifier value; Symbiosis; System; Techniques; Traction; Training; Variant; Virulence; Work; career; cohort; experience; extracellular; fascinate; fitness; flexibility; food biosecurity; gene function; homologous recombination; insight; microbial; microbiome; mutualism; pathogen; pathogenic bacteria; pressure; public health relevance; response; social; weapons

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.

描述（由申请人提供）：真核生物不断与大量不同微生物阵列相互作用。这些相互作用会以多方面的方式极大地影响双方伙伴的命运，演变和反应。了解细菌与真核生物之间的各种相互作用及其潜在的机制可以洞悉宿主抗性策略，细菌发病机理和相互合作。有趣的是，与非携带者对应物相比，已经证明了社会变形虫dictyostelium discoideum的载体克隆具有各种细菌。在宿主中，这些细菌提供食物和防御。在非载体克隆中，这些细菌是致病性的。 D. Discoideum适合各种生物学技术，可以被重要的人类病原体感染，并与各种微生物物种表现出不同的相互作用。这些属性使其成为探测真核生物 - 细菌接口的强大系统。我的研究的目的是定义D. discoideum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。我的具体目的是：1。确定载体和非载体dictyostelium discoideum变形虫克隆对细菌发病机理的差异反应。 2。检查变形虫 - 细菌共同进化对双方的影响。 3。识别涉及变形虫细菌界面的基因。通过这项工作，我将建立框架以更好地定义该模型系统，深入了解真核生物 - 微生物合作的发展和分解中的进化压力，并确定与宿主 - 微生物互助相关的基因。该灵活的系统可以进一步应用，以完善我们对指定感染与殖民/合作之间细线的进化途径以及差异宿主反应在这些事件中的作用的理解。最后，这项工作将为对变性菌 - 细菌界面所涉及的分子机制的更深入分析铺平道路，从而使沿更广泛的共生型连续体的跨国相互作用的动态原因和后果更加分辨。