Control of carbohydrate utilization in the prominent gut bacterium Bacteroides thetaiotaomicron

控制主要肠道细菌多形拟杆菌中碳水化合物的利用

• 批准号: 9757784
• 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 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9757784
• 关键词: Adopted; Animals; Bacterial Genes; Bacteroides; Bacteroides thetaiotaomicron; Carbohydrates; Carbon; Complex; DNA Binding; Diet; Dietary Carbohydrates; Elements; Elongation Factor; Enzymes; Escherichia coli; Exhibits; Forms Controls; Fucose; Gene Expression Regulation; Genes; Genetic Screening; Genetic Transcription; Genome; Glucose; Growth; Habits; Human; Individual; Intestinal Mucosa; Investigation; Mediating; Messenger RNA; Metabolic; Microbe; Molecular Conformation; Nutrient; Nutritional; Organism; Pathologic; Peptide Elongation Factor G; Peptide Hydrolases; Physiological; Play; Polysaccharides; PrP; Prions; Process; Production; Property; Proteins; Regulation; Regulatory Pathway; Reporter; Rho Factor; Role; Signal Transduction; Source; Structure; Surface; System; Thinness; Transcription Coactivator; Translations; commensal bacteria; experimental study; genetic regulatory protein; gut bacteria; gut colonization; gut microbiota; member; microbial; mutant; novel; paralogous gene; prion-like; response; termination factor; transcription termination; uptake

PROJECT SUMMARY This proposal examines the microbial responses to nutrients by investigating Bacteroides thetaiotaomicron, a prominent gut commensal bacterium that can grow on a large number of carbohydrates that humans and many other microbes cannot utilize. ~18% of the B. thetaiotaomicron's genome is predicted to mediate carbohydrate uptake and breakdown, and the regulation of these processes. This proposal seeks to identify the signals controlling four regulators of carbohydrate utilization, to define their regulated targets, and to establish how these proteins exert their regulatory actions. First, we will investigate the control of and by a master regulator of carbohydrate utilization implicated in gut colonization in several Bacteroides species. This aim also explores the role of a paralog of elongation factor EF-G that is under control of the master regulator, and like the master regulator, it is necessary for gut colonization and carbohydrate utilization. Second, we will examine how glucose, the preferred carbon source in most organisms, silences expression of a transcriptional activator necessary for gut colonization in a diet-dependent manner. And third, we will determine how the essential transcription termination factor Rho, which harbors a prion-like domain-containing element in B. thetaiotaomicron, adopts different forms and controls different sets of genes required for gut colonization and carbohydrate utilization. Our studies will reveal the mechanisms and hierarchies governing carbohydrate utilization, and elucidate the role of both of a prion-like domain in bacterial gene regulation. The proposed investigations may prove paradigmatic because they focus on atypical regulatory proteins. In addition, they may help explain what makes B. thetaiotaomicron a successful gut colonizer, and its abundance in lean healthy individuals.

项目概要 该提案通过调查拟杆菌来检查微生物对营养物质的反应 thetaiotaomicron，一种重要的肠道共生细菌，可以在大量的 人类和许多其他微生物无法利用的碳水化合物。约 18% B. thetaiotaomicron 的基因组预计可介导碳水化合物的摄取和分解，并且 对这些过程的监管。该提案旨在识别控制四个的信号 碳水化合物利用的监管者，定义他们的监管目标，并确定这些目标如何 蛋白质发挥其调节作用。首先，我们将研究master的控制 碳水化合物利用的调节剂与几种拟杆菌属肠道定植有关。 该目标还探讨了受 主调节器，与主调节器一样，它对于肠道定植和 碳水化合物的利用。其次，我们将研究葡萄糖（首选碳源）如何 大多数生物体，沉默肠道定植所需的转录激活因子的表达 以饮食依赖的方式。第三，我们将确定基本转录如何 终止因子 Rho，它在 B. thetaiotamicron，采用不同的形式并控制肠道所需的不同基因组 定植和碳水化合物利用。我们的研究将揭示其机制和 控制碳水化合物利用的层次结构，并阐明了朊病毒样的作用 细菌基因调控领域。拟议的调查可能被证明是范例 因为他们专注于非典型调节蛋白。此外，它们可能有助于解释什么 使 B. thetaiotaomicron 成为成功的肠道定殖者，其丰富的瘦肉健康成分 个人。