Control of gut colonization by the prominent gut bacterium Bacteroides thetaiotaomicron

著名肠道细菌多形拟杆菌对肠道定植的控制

• 批准号: 10646419
• 负责人: Eduardo Groisman
• 金额: $ 33.23万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-07 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10646419
• 关键词: Achievement; Bacteroides thetaiotaomicron; Biochemical; Biological; Carbohydrates; Complex; Diet; Dietary Sugars; Engineering; Escherichia coli; Fructose; GTP-Binding Proteins; Genes; Genetic Transcription; Glucose; Growth; Guanosine Triphosphate; Health; Human; In Vitro; Individual; Investigation; Liquid substance; Mediating; Messenger RNA; Mus; Nutrient; Peptide Elongation Factor G; Phase; Physical condensation; Polysaccharides; Property; Protein Biosynthesis; Proteins; Recycling; Research; Rho Factor; Ribosomes; Role; Signal Transduction; Starvation; Testing; Thinness; commensal bacteria; differential expression; genetic regulatory protein; gut bacteria; gut colonization; gut microbiota; in vivo; member; model organism; novel; paralogous gene; rho; sugar; termination factor; transcription termination; translation factor; uptake

PROJECT SUMMARY Bacteroides thetaiotaomicron is a beneficial gut bacterium strongly associated with lean and healthy individuals. This proposal seeks to understand how colonization of the mammalian gut by B. thetaiotaomicron is promoted by atypical forms of three highly conserved proteins: a paralog of the essential translation factor EF-G, designated EF-G2; the essential transcription termination factor Rho (BtRho), which harbors a ~300-residue long domain absent from canonical Rho proteins and specifically required for gut colonization; and Roc, a transcriptional regulator silenced by the simple sugars glucose and fructose. First, we will identify the biochemical properties of EF-G2 that distinguish it from EF-G and render it necessary for gut colonization, and test the hypothesis that EF-G2 is an energy-saving translation factor because it lacks the guanosine triphosphate hydrolyzing activity in the presence of vacant ribosomes that characterizes EF-G. Second, we will investigate the signals, genes, and regions of the extra domain that determine liquid-liquid phase separation in BtRho and identify genes regulated by the extra domain of BtRho. And third, we will determine how simple sugars control Roc amounts via the 5' leader region of the roc mRNA and identify genes controlled by Roc when B. thetaiotaomicron is in the murine gut. The proposed research will reveal novel biochemical activities for widespread proteins and uncover novel colonization determinants. Moreover, it will directly advance the engineering of commensal bacteria with desirable properties.

项目摘要 多形拟杆菌是一种有益的肠道细菌， 健康的个体。这项提议旨在了解哺乳动物肠道的殖民化是如何发生的。 由B。多形核被三种高度保守的蛋白质的非典型形式促进： 必需翻译因子EF-G的部分，命名为EF-G2;必需转录因子 终止因子Rho（BtRho），它含有一个约300个残基的长结构域， 典型的Rho蛋白，并且是肠道定植所特别需要的;和Roc，一种转录因子， 调节器沉默的单糖葡萄糖和果糖。首先，我们将确定 EF-G2的生物化学特性，使其与EF-G区分开来，并使其成为肠道所必需的 定植，并测试EF-G2是节能翻译因子的假设，因为它 在存在空核糖体的情况下缺乏鸟苷三磷酸水解活性， 表征EF-G。其次，我们将研究额外的信号，基因和区域。 决定BtRho中液-液相分离的结构域，并鉴定受 BtRho的额外结构域。第三，我们将确定单糖如何控制Roc量 通过roc mRNA的5'前导区，鉴定当B. 多形核在鼠的肠道中。这项拟议中的研究将揭示新的生化 活性广泛的蛋白质和发现新的殖民决定因素。而且将 直接推进具有所需性质的微生物细菌的工程化。