Regulation and Function of a Mutualistic Bacterial Host Range Specificity Determinant

共生细菌宿主范围特异性决定因素的调节和功能

• 批准号: 1353674
• 负责人: Katrina Forest
• 金额: $ 72.5万
• 依托单位: University of Wisconsin-Madison
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1353674&HistoricalAwards=false
• 关键词: Regulation; Function; Mutualistic; Bacterial; Host

All plant and animal hosts associate with microbial symbionts that can contribute to health or cause disease. Many microbe-host associations (both beneficial and pathogenic) are specific; only a single species or strain of microbe exists in close association with a single host or tissue. A fundamental but unanswered biological question is what allows some microbes but not others to colonize specific hosts or tissues. This research investigates how bacteria and animal symbiotic partners recognize each other while excluding unwanted species. The bacterium being studied colonizes the intestine of a small soil-dwelling roundworm (nematode) , and expresses traits beneficial for the nematode. The project focuses on a bacterial membrane protein that is necessary for colonization and dictates specificity for certain nematode species. This protein represents a family of proteins present in many symbionts that colonize animal mucosae. Genetic, biochemical, physical, and microscopy approaches will be used to reveal the structure, biochemical function, and interacting host factors of the protein. In general, the work will hasten technical advances for investigating an understudied class of membrane proteins. Also, the research will provide paradigms that yield broad insights into the molecular basis of microbial colonization of animals and what might allow microbes to expand beyond their current colonization ranges and enter new hosts or tissue sites. The public will be exposed to this research through community seminars and high school outreach programs. The project encompasses the NSF-recommended five core concepts for undergraduate education, and will be used to generate an integrated curriculum emphasizing these areas. Undergraduate, graduate, and post-doctoral apprentices will be trained in the areas of structural biology, molecular biology, nematology, and bacteriology through direct scientific inquiry. Thus, this project will provide fundamental knowledge of bacterial interactions with animal hosts, and will help train future scientists with expertise to further apply this knowledge.

所有动植物宿主都与有助于健康或导致疾病的微生物共生体有关。许多微生物-宿主组合(包括有益的和致病的)都是特定的；只有一种微生物或菌株与单一宿主或组织密切相关。一个基本但尚未回答的生物学问题是，是什么允许一些微生物而不是其他微生物在特定的宿主或组织中定居。这项研究调查了细菌和动物共生伙伴如何在排除不需要的物种的同时识别彼此。正在研究的细菌在一种小型土栖蛔虫(线虫)的肠道中定居，并表现出有利于线虫的特征。该项目的重点是一种细菌膜蛋白，它是定植所必需的，并决定了某些线虫物种的特异性。这种蛋白质代表了存在于许多定植于动物粘膜的共生体中的一组蛋白质。将使用遗传、生化、物理和显微方法来揭示蛋白质的结构、生化功能和相互作用的宿主因素。总体而言，这项工作将加速研究一类未被研究的膜蛋白的技术进步。此外，这项研究将提供范例，对动物微生物定植的分子基础以及什么可能允许微生物超越目前的定植范围并进入新的宿主或组织部位产生广泛的见解。公众将通过社区研讨会和高中外展计划接触到这项研究。该项目包括NSF推荐的本科教育的五个核心概念，并将用于生成强调这些领域的综合课程。本科生、研究生和博士后学徒将通过直接的科学研究在结构生物学、分子生物学、线虫学和细菌学领域接受培训。因此，该项目将提供细菌与动物宿主相互作用的基本知识，并将有助于培训具有进一步应用这些知识的专业知识的未来科学家。