Hierachy Within Environmental Regulons

环境调节子内的层次结构

• 批准号: 6631829
• 负责人: RONALD K TAYLOR
• 金额: $ 27.65万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-06-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6631829
• 关键词: Vibrio cholerae; bacterial genetics; biological signal transduction; cholera toxin; gene expression; genetic promoter element; genetic regulatory element; host organism interaction; laboratory mouse; virulence

DESCRIPTION (provided by the applicant): Infection by bacterial pathogens continues to be a major health concern throughout the world. For example, during the past decade the incidence of cholera spread to more areas of the globe than had occurred in the previous 100 years. A better understanding of the molecular bases of pathogenesis may provide new ways to combat bacterial infection. The goal of this research is to discern the mechanisms by which physiological signals in the environment within the human host are converted to molecular interactions that govern the expression of virulence genes of the infecting bacterium. The model system to be analyzed is the Vibrio cholerae ToxR virulence regulon, for which a number of parameters that influence gene expression, as well as many of the regulators and target genes, are known and partially characterized. The target virulence genes include the tcp operon, toxT, and other "ToxR activated" genes present on the Vibrio cholerae TCP pathogenicity island, as well as the ctx operon present on a lysogenic bacteriophage. The regulators are encoded by genes distributed around the genome, including toxRS, aph.4, aphB, hns, and crp, as well as the tcpPH and toxT genes present on the pathogenicity island. It has recently been determined that multiple regulators function at each target gene promoter. The current proposal focuses on a subset of target promoters and regulators to understand how these regulators function in an interaction with growth condition signals, the promoters, and with each other to control gene expression. In addition, the identity of additional target genes for which expression is influenced by the regulatory proteins that are not encoded within the Vibrio TCP pathogenicity island will help to better understand the precise chemical and physical responses that are being converted into virulence gene expression mechanisms. Correlating virulence gene expression together with regulatory responses that modulate bacterial physiology represents a new approach that utilizes knowledge of the genome to further our understanding of the basis of virulence gene regulation. Finally, new approaches to monitor virulence gene expression both in vitro and in vivo will provide a means to correlate these two events and to identify additional genes involved in regulation. These experiments will likely reveal novel virulence factor genes that may prove to be useful vaccine or therapeutic targets. A further understanding of virulence gene expression will also help in the development of ways to modulate it either in vivo or in vitro for improved vaccine production or overproduction of virulence factors for structural analyses.

性状（由申请方提供）：细菌性病原体感染 仍然是全世界的一个主要健康问题。比如说， 在过去的十年中，霍乱的发病率蔓延到更多的地区， 地球仪比过去100年都要大。更好地了解 致病的分子基础可能提供新的方法来对抗细菌， 感染这项研究的目标是找出导致这种情况的机制 人体内环境中的生理信号被转换成 分子相互作用，支配的毒力基因的表达， 感染细菌待分析的模型系统是霍乱弧菌 ToxR毒力调节子，对于该调节子，影响基因表达的许多参数都是重要的。 表达以及许多调节因子和靶基因是已知的， 部分特征。靶毒力基因包括tcp操纵子， toxT和存在于霍乱弧菌TCP上的其它“ToxR激活”基因 致病岛，以及存在于溶原性 噬菌体调节器由分布在细胞周围的基因编码。 基因组，包括toxRS，aph.4，aphB，hns和crp，以及tcpPH和 毒力岛上存在toxT基因。最近已经确定 多个调节子在每个靶基因启动子处起作用。当前 提案侧重于目标发起人和监管机构的子集，以了解 这些调节剂如何在与生长条件信号的相互作用中起作用， 启动子，并与彼此控制基因表达。此外该 其表达受所述靶基因影响的其它靶基因的身份 在Vibrio TCP致病性内不编码的调节蛋白 岛将有助于更好地了解精确的化学和物理 这些反应被转化为毒力基因表达机制。 将毒力基因表达与调控反应相关联， 调节细菌生理学代表了一种新的方法， 以进一步了解毒力基因的基础 调控最后，监测毒力基因表达的新方法， 将提供一种使这两种事件相关的方法， 确定参与调控的其他基因。这些实验很可能 揭示新的毒力因子基因，可能被证明是有用的疫苗或 治疗目标对毒力基因表达的进一步了解将有助于 也有助于开发体内或体外调节它的方法 用于改进疫苗生产或过量生产毒力因子 结构分析。