Regulation of Host Colonization Specificity

宿主定植特异性的调节

• 批准号: 1456963
• 负责人: Mark Mandel
• 金额: $ 63.64万
• 依托单位: Northwestern University at Chicago
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2017-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1456963&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.

细菌在动物宿主体内定植并发挥重要作用。人们对与特定动物宿主相关的细菌有了越来越多的了解，但特定动物被特有的有益细菌定植并避免被有害（致病）细菌定植的过程和机制尚不清楚。这个项目使用了一个简化的系统，在这个系统中，一个动物器官只被一种细菌定植，作为一种检查这些过程和机制的方法。分子遗传学方法将用于鉴定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，细菌聚集是一个容易发生的过程，对细菌在自然和人为环境中发挥有益或有害功能的能力具有广泛的影响。气候变化已被证明会影响细菌与动物的关系，因此，对这些相互作用的分子基础有更深入的了解，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，传染病的进化取决于病原体与动物宿主的相互作用，因此辨别影响微生物-宿主交流的调节变化至关重要。学生将接受现代遗传学、基因组学和生物信息学方面的培训，以解决“大数据”问题。外展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，对伴侣双方的健康和发育至关重要。这些关系已经进化出强大的机制，以确保共生体在每一代新的宿主中忠实地传播。本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。该项目重点研究了费氏弧菌与短尾鱿鱼宿主之间的二元关联。初步数据揭示了生物膜形成（细菌聚集）在宿主定植过程中的重要性，无论是在乌贼的V. fischeri定植中还是在许多细菌定植系统中。在典型的鱿鱼共生体ES114中，RscS组氨酸激酶激活了正常宿主定植所必需的生物膜基因。一种比较方法确定了不使用RscS进行定植的菌株，在该项目中，分子遗传学方法将用于确定密切相关的共生菌株中调节聚集和定植的信号转导途径。通过采用包含自然种群、基因组、途径和基因的综合方法，该项目将产生对维持共生-宿主保真度的分子机制的理解，并促进水平传播细菌共生体的共同进化动力学。结合研究目标，提出了一个试点工作坊，培养本科生和研究生的现代生物信息学技术。