Campylbacter jejuni flagellar regulation and synthesis

空肠弯曲菌鞭毛调节与合成

• 批准号: 8500109
• 负责人: DAVID R HENDRIXSON
• 金额: $ 37.37万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8500109
• 关键词: Anabolism; Animals; Bacteria; Bacterial Gastroenteritis; Binding Proteins; Biochemical; Biological Models; Biology; Birds; C-terminal; Campylobacter jejuni; Cells; Cellular biology; Centers for Disease Control and Prevention (U.S.); Complex; Country; DNA; DNA Binding; Development; Disease; Ensure; Escherichia coli; Family; Flagella; Food Supply; Gastroenteritis; Gastrointestinal tract structure; Gene Expression; Genes; Genetic; Genetic Transcription; Guanosine Triphosphate Phosphohydrolases; Helicobacter; Human; Infection; Intestines; Link; Mastigophora; Mediating; Messenger RNA; Molecular; Organelles; Organism; Pathway interactions; Phosphorylation; Phosphotransferases; Prevention; Production; Protein C; Proteins; Pseudomonas; Regulation; Regulon; Relative (related person); Research; Role; Salmonella; Signal Pathway; Signal Transduction; Specificity; Symbiosis; System; Systems Analysis; Technology; Testing; Therapeutic; United States; Vibrio; Virulence; Work; acetyl phosphate; base; cell motility; computerized data processing; factor C; genetic regulatory protein; in vitro Model; in vivo; insight; interest; member; novel; pathogen; prevent; programs; sensor; tool

DESCRIPTION (provided by applicant): Campylobacter jejuni is a leading cause of gastroenteritis in humans in the United States and in other countries throughout the world. According to the Centers for Disease Control, C. jejuni competes with Salmonella species as the leading cause of bacterial gastroenteritis in the United States. In contrast, C. jejuni is a common commensal organism of the gastrointestinal tracts of wild and agriculturally-important animals, which contributes to the large amount of C. jejuni found in the human food supply leading to sporadic cases of disease. Flagellar motility is the only proven virulence and colonization factor of C. jejuni, required to promote infection of humans and avian species for the development of disease or commensalism. C. jejuni produces a single flagellum at one or both poles of the bacterium. Thus, C. jejuni belongs to a significant group of bacterial pathogens, such as Vibrio, Pseudomonas, and Helicobacter species, that are programmed to produce a limited number of flagella and place these organelles only at the poles, unlike more commonly studied peritrichous bacteria such as E. coli and Salmonella species. We have used C. jejuni as a model system to understand regulation of flagellar gene expression and biosynthesis in polarly-flagellated bacterial pathogens. This regulatory system requires the flagellar export apparatus, the FlgSR two-component system and the FlhF GTPase for expression C54-dependent flagellar genes. In addition, FlhF and the putative ATP- binding protein, FlhG, are required for proper flagellar placement, number, or biosynthesis with FlhG possessing an additional function in septation. The objectives of this proposal are to analyze signaling processes in C. jejuni that mediate proper expression of flagellar genes while using the flagellar regulatory system to promote a deeper understanding into the cellular biology of signaling networks, complex organelle development, and bacterial septation. In Aim 1, we will analyze a novel signaling mechanism occurring between the flagellar export apparatus and the FlgS sensor kinase that leads to activation of the FlgSR system. In Aim 2, we will analyze the biology of FlgR, an NtrC-like protein, which contains a unique C- terminus that allows for a likely alternative mechanism of signal transduction and transcriptional initiation. In Aim 3, we will analyze how FlhF influences flagellar gene expression and biosynthesis and the dual functions of FlhG in controlling polar flagellar number and septation. Accomplishment of these aims will aid in understanding: 1) a unique molecular mechanism of signaling between protein systems in bacteria; 2) alternative mechanisms of transcriptional initiation for an NtrC-like protein; 3) how signaling networks in bacteria are insulated from each other to mediate specificity of signaling; 4) complex organelle development; and 5) aspects of bacterial septation.

描述（由申请方提供）：空肠弯曲菌是美国和世界其他国家人类胃肠炎的主要病因。根据疾病控制中心的数据，C。在美国，空肠杆菌与沙门氏菌竞争成为细菌性胃肠炎的主要原因。与之相反，C.空肠是野生动物和重要农业动物胃肠道的常见寄生生物，其导致大量的C.在人类食物供应中发现的空肠导致零星的疾病病例。鞭毛运动是唯一被证实的C.空肠，需要促进人类和禽类感染以发展疾病或寄生虫病。C.空肠在细菌的一极或两极产生单个鞭毛。因此，C. jejuni属于一组重要的细菌病原体，如弧菌属、假单胞菌属和螺杆菌属，它们被编程为产生有限数量的鞭毛，并将这些细胞器仅放置在两极，这与更常见的研究的周毛细菌如E.大肠杆菌和沙门氏菌属。我们使用C。空肠作为一个模型系统，以了解鞭毛基因的表达和生物合成的调控极鞭毛细菌病原体。这一调控系统需要鞭毛输出装置、FlgSR双组分系统和FlhF GTdR来表达C54依赖的鞭毛基因。此外，FlhF和推定的ATP结合蛋白FlhG是鞭毛适当放置、数量或生物合成所需的，FlhG在分隔中具有额外的功能。本文的目的是分析C语言中的信号传递过程。空肠，介导鞭毛基因的正确表达，同时使用鞭毛调节系统，以促进对信号网络，复杂的细胞器发育和细菌分隔的细胞生物学的更深入的理解。在目标1中，我们将分析一种新的信号转导机制之间发生的鞭毛出口装置和FlgS传感器激酶，导致激活的FlgSR系统。在目标2中，我们将分析FlgR的生物学，FlgR是一种NtrC样蛋白，其含有独特的C末端，其允许信号转导和转录起始的可能的替代机制。目的3：分析FlhF对鞭毛基因表达和生物合成的影响，以及FlhG在控制极鞭毛数量和分隔中的双重功能。这些目标的实现将有助于理解：1）细菌中蛋白质系统之间信号传导的独特分子机制; 2）NtrC样蛋白质转录起始的替代机制; 3）细菌中的信号传导网络如何彼此绝缘以介导信号传导的特异性; 4）复杂的细胞器发育;以及5）细菌分隔的方面。