Signal Transduction Response in Helicobacter pylori

幽门螺杆菌的信号转导反应

• 批准号: 6556035
• 负责人: MARK H FORSYTH
• 金额: $ 13.38万
• 依托单位: COLLEGE OF WILLIAM AND MARY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-15 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6556035
• 关键词: Helicobacter; bacterial genetics; biological signal transduction; enzyme activity; gene complementation; gene environment interaction; gene expression; gene mutation; genetic mapping; genetic regulation; genetic regulatory element; genetic strain; histidine; immunoelectron microscopy; microarray technology; nucleic acid sequence; operon; pathologic process; peptide chemical synthesis; recombinant proteins; regulatory gene; transcription factor; urease

DESCRIPTION (provided by applicant): Genome sequencing of numerous prokaryotes has revealed a tendency toward decreased genetic investment in signal transduction machinery in species that exist in restricted ecological niches. Bacterial signal transduction systems are typically comprised of a sensory histidine kinase protein and a cognate transcription factor, known as a response regulator. Bacterial species capable of growth in multiple environments have large numbers of signal transduction systems, as many as 63 separate systems. Bacteria that are restricted to a pathogenic lifestyle and have no known environmental reservoir possess many fewer systems to detect and respond to environmental changes. Helicobacter pylori, the etiologic agent of peptic ulcer disease as well as gastric adenocarcinoma, appears to inhabit exclusively the human gastric mucosa. Genome sequencing of this bacterium reveals only 4 signal transduction pathways. This implies a somewhat limited repetoire of signals to which this pathogen can respond. This proposal takes advantage of the complete genetic characterization of two distinct pathogenic strains of H. pylori to examine the role of one specific signal transduction system in the control of gene expression. The studies described here will facilitate the determination of signals in the gastric ecosystem that serve as cues for H. pylori to alter its gene expression pattern. This will be accomplished by identifying genes used in the adaptive response to these environmental signals. These studies will utilize H. pylori mutants which are "blinded" to an aspect of their environment due to the targeted destruction of genes encoding a sensory protein. Utilizing whole-genome transcriptional profiling by means of DNA microarrays, the regulatory events comprising the adaptive response in this gastric pathogen will be mapped and the genes of the adaptive response will be characterized. Determination of the identity of genes whose transcription is regulated will allow potential environmental cues to be inferred and then experimentally determined. Similarly, use of recombinant transcription factors (response regulators) will allow the isolation of critical DNA sequences necessary to accomplish regulation of gene expression. Understanding of the gastric environment, as perceived though the sensory apparatus of H. pylori, will allow a better understanding of H. pylori pathogenesis and a more rational design of interventions into the infectious process.

描述（由申请人提供）：众多原核生物的基因组测序表明，在受限制的生态壁ches中存在的物种中信号转导机械中遗传投资的趋势降低。细菌信号转导系统通常由感觉组氨酸激酶蛋白和同源转录因子（称为响应调节剂）组成。能够在多种环境中生长的细菌物种具有大量的信号转导系统，多达63个独立的系统。仅限于致病生活方式且没有已知环境储层的细菌具有较少的系统来检测和应对环境变化。幽门螺杆菌是消化性溃疡疾病和胃腺癌的病因学药物，似乎完全居住在人类胃粘膜中。该细菌的基因组测序仅显示4个信号转导途径。这意味着该病原体可以反应的信号的重复有限。该建议利用了幽门螺杆菌的两种不同致病菌株的完整遗传表征，以检查一个特定信号转导系统在控制基因表达中的作用。此处描述的研究将促进胃生态系统中信号的确定，这些信号是幽门螺杆菌改变其基因表达模式的线索。这将通过确定对这些环境信号的自适应响应中使用的基因来实现。这些研究将利用幽门螺杆菌突变体，这些突变体被“蒙蔽”到其环境方面，这是由于编码感觉蛋白的基因的靶向破坏。通过DNA微阵列利用全基因组转录分析，将绘制包含该胃病原体自适应反应的调节事件，并将描绘自适应反应的基因。调节转录的基因身份的确定将允许推断潜在的环境线索，然后通过实验确定。同样，使用重组转录因子（响应调节剂）将允许分离临界DNA序列，以完成基因表达的调节。通过感知到幽门螺杆菌的感觉仪，对胃环境的理解将可以更好地理解幽门螺杆菌的发病机理，并更合理地将干预措施设计为传染性过程。