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.

项目摘要 该建议通过调查拟杆菌来研究微生物对营养物质的反应 thetaiotaomicron，一种突出的肠道细菌，可以在大量的 碳水化合物，人类和许多其他微生物不能利用。~18%的B。 据预测，多形核的基因组介导碳水化合物的摄取和分解， 这些过程的规范。该建议旨在确定控制四个信号 碳水化合物利用的调节剂，以确定其调节的目标，并建立如何这些 蛋白质发挥它们的调节作用。首先，我们将研究主人的控制和主人的控制 在几种拟杆菌属物种的肠道定殖中涉及的碳水化合物利用的调节剂。 这一目的还探讨了一个在细胞外基质中的延伸因子EF-G的作用。 主调节器，并且像主调节器一样，它是肠道定植所必需的， 碳水化合物利用第二，我们将研究葡萄糖，首选的碳源， 大多数生物体，沉默表达的转录激活必需的肠道定植 以饮食依赖的方式。第三，我们将确定基本转录 终止因子Rho，其在B中具有含朊病毒样结构域的元件。 多形核，采用不同的形式，并控制肠道所需的不同基因组 定殖和碳水化合物利用。我们的研究将揭示其机制， 控制碳水化合物利用的层次结构，并阐明朊病毒样 结构域在细菌基因调控中的作用。拟议的调查可能证明是典型的 因为他们专注于非典型的调节蛋白。此外，它们可能有助于解释 是B。thetaiotaomicron是一种成功的肠道定植者，其丰富的瘦肉健康 个体