Regulation of Host Colonization Specificity

宿主定植特异性的调节

• 批准号: 1757297
• 负责人: Mark Mandel
• 金额: $ 34.28万
• 依托单位: University of Wisconsin-Madison
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2019-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1757297&HistoricalAwards=false
• 关键词: Regulation; Host; Colonization; Specificity

Bacteria colonize and perform critical functions for their animal hosts. There has been an increased understanding of the bacteria that are associated with specific animal hosts, but the proceses and mechanisms by which specific animals become colonized with characteristic beneficial bacteria and avoid colonization by harmful (pathogenic) bacteria are not well-understood. This project uses a simplified system in which an animal organ is colonized by only a single bacterial species as a way to examine these processes and mechanisms. Molecular genetic approaches will be used to identify bacterial genes and processes that are critical to host colonization, and comparative approaches will be used to determine how the gene circuits in different bacteria evolve to either keep the same animal partner or allow the bacteria to switch and colonize a new animal host. This work has the potential to impact studies of bacterial aggregation, a process that occurs readily and has broad implications for the ability of bacteria to perform beneficial or harmful functions in natural and man-made environments. Climate change has been shown to influence bacterial-animal associations, so a deeper understanding of the molecular basis to these interactions will allow us to better prepare for changing environmental conditions. Finally, the evolution of infectious diseases depends on pathogen interactions with animal hosts, and therefore it is critical to discern regulatory changes that influence microbe-host communication. Students will be trained in modern genetics and genomics, and bioinformatics to address "big data" questions. Outreach activities are focused on broadening the representation of future STEM field leaders. Microbial symbioses are prevalent in animals and are crucial to the health and development of both partners. These relationships have evolved robust mechanisms to ensure the faithful transmission of symbionts during each new host generation. This project applies modern genomic and genetic methods to examine how host specificity develops in a horizontally transmitted animal-microbe symbiosis. The project focuses on the binary association between Vibrio fischeri bacteria and the bobtail squid hosts. Preliminary data have revealed the importance of biofilm formation (bacterial aggregation) during host colonization, both in V. fischeri colonization of squid and in many bacterial colonization systems. In the canonical squid symbiont ES114, the RscS histidine kinase activates biofilm genes that are necessary for normal host colonization. A comparative approach identified strains that do not use RscS for colonization, and in the project molecular genetic approaches will be undertaken to identify the signal transduction pathways regulating aggregation and colonization in closely related symbiont strains. By taking an integrative approach that encompasses natural populations, genomes, pathways, and genes, the project will yield an understanding of the molecular mechanisms that maintain symbiont-host fidelity and facilitate co-evolutionary dynamics in horizontally-transmitted bacterial symbionts. A pilot workshop is proposed that integrates with the research aims and trains undergraduate and graduate students in modern bioinformatics techniques.

细菌在动物宿主中定植并发挥关键作用。人们对与特定动物宿主相关的细菌有了更多的了解，但特定动物被特征性有益细菌定殖并避免有害（致病）细菌定殖的过程和机制还没有很好地了解。该项目使用一个简化的系统，其中动物器官仅由单一细菌物种定殖，作为检查这些过程和机制的一种方式。分子遗传学方法将用于识别对宿主定植至关重要的细菌基因和过程，比较方法将用于确定不同细菌中的基因回路如何进化，以保持相同的动物伴侣或允许细菌切换并定植新的动物宿主。这项工作有可能影响细菌聚集的研究，这一过程很容易发生，并对细菌在自然和人造环境中发挥有益或有害功能的能力产生广泛影响。气候变化已被证明会影响细菌-动物的关系，因此更深入地了解这些相互作用的分子基础将使我们能够更好地为不断变化的环境条件做好准备。最后，传染病的演变取决于病原体与动物宿主的相互作用，因此，识别影响微生物-宿主交流的调控变化至关重要。学生将接受现代遗传学和基因组学以及生物信息学的培训，以解决“大数据”问题。外联活动的重点是扩大未来STEM领域领导者的代表性。微生物共生在动物中普遍存在，对双方的健康和发展至关重要。这些关系已经发展出强大的机制，以确保在每一代新的主机共生体的忠实传输。该项目应用现代基因组学和遗传学方法来研究宿主特异性如何在水平传播的动物-微生物共生中发展。该项目的重点是费氏弧菌细菌和短尾鱿鱼宿主之间的二元关联。初步数据显示，生物膜形成（细菌聚集）的重要性，在宿主定植，无论是在V. fischeri定殖鱿鱼和许多细菌定殖系统。在典型的鱿鱼共生体ES 114中，RscS组氨酸激酶激活正常宿主定殖所必需的生物膜基因。一种比较方法确定了不使用RscS定植的菌株，在该项目中，将采用分子遗传学方法来确定调节密切相关的共生体菌株中聚集和定植的信号转导途径。通过采取包括自然种群，基因组，途径和基因的综合方法，该项目将产生维持共生体-宿主保真度的分子机制的理解，并促进水平传播的细菌共生体的共同进化动力学。一个试点讲习班，提出了与研究目标相结合，培养本科生和研究生在现代生物信息技术。