VIBRIO GENE EXPRESSION DURING INFECTION

感染期间的弧菌基因表达

• 批准号: 2672845
• 负责人: Andrew Camilli
• 金额: $ 11.66万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-01 至 2002-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2672845
• 关键词: Vibrio cholerae; bacterial cytopathogenic effect; bacterial genetics; bacterial proteins; electroporation; gastrointestinal infection; gene deletion mutation; gene expression; host organism interaction; infant animal; laboratory mouse; molecular cloning; northern blottings; operon; vibriosis; virulence

DESCRIPTION (Adapted from the applicant's abstract): The pathogenicity of Vibrio cholerae, which infects mucosal surfaces in the small intestine, is believed to be a coordinated and multifactorial process. Unfortunately, knowledge of which genes are expressed during infection, as well as the regulatory proteins and host signals that govern their regulation, is rudimentary. A novel gene reporter system has been constructed for identifying in vivo induced genes of V. cholerae, and has been used to identify the vie (V. cholerae in vivo expressed) operon. vie is predicted to encode three two-component signal transduction proteins, including a sensor and two response regulators, the first such system described in V. cholerae. vie is unique among such systems both in its operon structure and its exclusive expression during infection. Based on analogy to other systems, it is hypothesized that the Vie proteins function by sensing environmental conditions in the host intestine and responding by regulating other genes. Characterization of vie thus provides a unique opportunity both to probe the host signals and bacterial regulatory proteins that control V. cholerae growth and pathogenicity as well as to allow investigation of vie-regulated genes. The goals of this research proposal are to characterize the vie operon and to identify and characterize vie-regulated genes. Mutations will be constructed in both vie and vie-regulated genes, and the effects of each on pathogenicity will be measured. The subcellular locations of the Vie proteins will be determined using immunochemical methods. The spatial and temporal expression patterns of the vie operon and vie-regulated genes will be determined during infection. This work may contribute to development of mucosal vaccines and to identification of new targets for therapies against mucosal pathogens.

描述（改编自申请人的摘要）： 感染小肠粘膜表面的弧菌霍乱是 被认为是协调的多因素过程。 很遗憾， 了解哪些基因在感染期间表达了哪些基因 监管其监管的监管蛋白和宿主信号是 基本。 已经为一个新颖的基因报道系统构建了 识别霍乱弧菌的体内诱导基因，并已用于 识别VIE（V. Cholerae in Vivo表示）操纵子。 预测VIE 编码三个两分量信号转导蛋白，包括A 传感器和两个响应调节器，第一个中描述的第一个系统。 霍乱。 VIE在操纵子结构和此类系统中都是独一无二的 它在感染过程中的独家表达。 基于与其他的类比 系统，假设VIE蛋白通过传感功能 宿主肠中的环境条件并通过调节而做出反应 其他基因。 因此，VIE的特征提供了独特的机会 探测宿主信号和细菌调节蛋白 控制V.霍乱的生长和致病性以及允许 研究VIE调节的基因。 该研究建议的目标 要表征VIE操纵子并识别和表征 VIE调节的基因。 突变将在VIE和 VIE调节的基因以及每种基因对致病性的影响将是 测量。 VIE蛋白的亚细胞位置将确定 使用免疫化学方法。 空间和时间表达模式 VIE操纵子和VIE调节的基因将在期间确定 感染。 这项工作可能有助于粘膜疫苗的开发和 确定针对粘膜病原体疗法的新靶标。