Citrobacter illuminates the mechanistic underpinnings of gut biogeography

柠檬酸杆菌阐明了肠道生物地理学的机制基础

基本信息

批准号：
10198730
负责人：
Andreas J Baumler
金额：
$ 22.59万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10198730
关键词：
Animal Model Citrobacter Citrobacter rodentium Collection Data Ecosystem Engineering Environment Environmental Risk Factor Epithelial Equilibrium Etiology Extinction (Psychology)Foundations Goals Growth Habitats Health Homeostasis Human Hydrogen Peroxide Infection Light Mediating Microbe Modeling Mucous Membrane Mucous body substance Mus Nutrient Nutritional Oxygen Pathogenesis Phase Play Process Research Research Personnel Resources Role Shapes Structure Surface Testing Type III Secretion System Pathway Virulence Virulence Factors Work colon microbiota dysbiosis enteric pathogen expectation genetic manipulation gut microbiota host microbiota host-associated microbial communities human disease innovation insight interest knowledge of results microbial microbial community microbiome research microbiota novel pathogen prevent public health relevance tool trait

项目摘要

PROJECT SUMMARY The microbiota influences many aspects of human health, but the mechanisms that balance it remain incompletely understood. Our previous work has established the concept that enteric pathogens act as ecosystem engineers by using their virulence factors to manipulate host habitat filters, thereby constructing new nutrient-niches that support their invasion of the gut ecosystem. Thus, mucosal pathogens are valuable tools for identifying host-derived habitat filters that structure the microbiota. Our long-range goal is to identify host-derived habitat filters that shape the microbiota by using Citrobacter rodentium as a tool to identify environmental factors that allow the pathogen to edge out gut-associated microbial communities. The objectives of this application are to study how its main virulence factor, the type III secretion system (T3SS), helps C. rodentium to prevent pathogen extinction during the initial phase of infection. Our central hypothesis is that virulence factors provide C. rodentium with access to epithelial hydrogen peroxide, a host habitat filter that sustains pathogen growth early after infection. We will test different aspects of our hypothesis by determining whether intimate attachment mediated by the T3SS provides C. rodentium access to NOX1-derived hydrogen peroxide (H2O2) and determining the role NOX1-derived H2O2 plays as a habitat filter structuring the spatial organization of the gut microbiota. The proposed work makes innovative use of mucosal pathogens to provide fundamental insights into microbiome research and we expect that a successful completion will offer mechanistic insights into host habitat filters selecting for microbial traits that permit survival and growth in the host. By establishing the identity of a novel host-derived habitat filter, our research will be of wide appeal among researchers interested in microbial pathogenesis and the nutritional environment that shapes our host-associated microbial communities.

项目摘要微生物群会影响人类健康的许多方面，但是平衡它的机制仍然存在不完全理解。我们以前的工作已经确定了肠道病原体的概念生态系统工程师通过使用其毒力因素来操纵宿主栖息地过滤器，从而建造新的支持其入侵肠道生态系统的营养因素。因此，粘膜病原体是有价值的工具识别构造微生物群的宿主衍生的栖息地过滤器。我们的远程目标是确定宿主的衍生栖息地过滤了通过使用柠檬酸杆菌作为识别环境因素的工具来塑造微生物群的过滤这使病原体可以远离肠道相关的微生物群落。此应用程序的目标是为了研究其主要毒力因素如何，III型分泌系统（T3SS）有助于啮齿动物C.防止在感染的初始阶段，病原体灭绝。我们的中心假设是毒力因素提供 C.啮齿动物C. c. and访问上皮氢过氧化感染后。我们将通过确定是否依恋来检验假设的不同方面由T3SS介导的啮齿动物C. rodentium访问NOX1衍生的过氧化氢（H2O2）和确定NOX1衍生的H2O2的作用是构成肠道空间组织的栖息地过滤器微生物群。拟议的工作使创新使用粘膜病原体，以提供基本的见解微生物组研究，我们预计成功完成将为宿主栖息地提供机械洞察力过滤器选择允许宿主存活和生长的微生物性状。通过建立一个身份新型宿主衍生的栖息地过滤器，我们的研究将在对微生物感兴趣的研究人员中具有广泛的吸引力发病机理和营养环境塑造了我们宿主相关的微生物群落。