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: 10444020
• 负责人: Eduardo Groisman
• 金额: $ 33.73万
• 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/10444020
• 关键词: Achievement; Animal Model; 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; Polysaccharides; Property; Protein Biosynthesis; Proteins; Recycling; Research; Rho Factor; Ribosomes; Role; Savings; Signal Transduction; Starvation; Testing; Thinness; commensal bacteria; differential expression; genetic regulatory protein; gut bacteria; gut colonization; gut microbiota; in vivo; member; 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.

项目概要 多形拟杆菌是一种有益的肠道细菌，与瘦肉和瘦肉密切相关。 健康的个体。该提案旨在了解哺乳动物肠道的定植是如何进行的 B. thetaiotaomicron 的作用是由三种高度保守的蛋白质的非典型形式促进的： 必需翻译因子 EF-G 的旁系同源物，指定为 EF-G2；基本转录 终止因子 Rho (BtRho)，含有约 300 个残基的长结构域， 典型的 Rho 蛋白，是肠道定植所必需的；和 Roc，转录 调节剂被单糖葡萄糖和果糖沉默。首先，我们将确定 EF-G2 的生化特性使其与 EF-G 不同，并使其成为肠道必需的 定植，并检验 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三磷酸鸟苷水解活性 EF-G 的特点。其次，我们将研究额外的信号、基因和区域。 确定 BtRho 中液-液相分离的结构域并识别受 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' 前导区并识别 B. thetaiotamicron 位于小鼠肠道中。拟议的研究将揭示新的生化 广泛蛋白质的活性并揭示新的定植决定因素。而且，它将 直接推进具有所需特性的共生细菌的工程。