REGULATION OF PS AERUGINOSA GENES DURING INFECTION

感染期间铜绿假单胞菌基因的调节

• 批准号: 2887160
• 负责人: SHOUGUANG JIN
• 金额: $ 2.74万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-15 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2887160
• 关键词: Pseudomonas aeruginosa; bacterial genetics; cystic fibrosis; exotoxins; gene expression; gene rearrangement; gene targeting; genetic regulation; genetically modified animals; host organism interaction; human tissue; laboratory mouse; lipopolysaccharides; molecular cloning; opportunistic infections; restriction mapping; virulence

DESCRIPTION (Adapted from applicant's abstract): Pseudomonas aeruginosa, an opportunistic pathogen, is the major causative agent of mortality and morbidity in immunocompromised patients. It is also the most important pathogen of patients with cystic fibrosis. During chronic infection, numerous changes have been identified including repression of specific virulence genes and surface changes. In order to identify virulence genes of P. aeruginosa that are important in the infection of CF patients, Dr. Jin developed a selection system similar to the in vivo expression technology first described in Salmonella. Using this system, he has identified three genetic loci that are inducible by tracheal-bronchial mucus from CF patients. These loci include the pyochelin receptor, the migA/B locus which is homologous to genes involved in LPS synthesis and is controlled by a DNA rearrangement switch, and regA a positive regulator of exotoxin A synthesis. In this application, Dr. Jin proposes to focus on the migA/B locus and test the hypothesis that the DNA rearrangement in the migA/B locus is responsible for the LPS and exotoxin A phase variation observed in chronic infection. Experiments are designed to (i) define the function of the migA/B gene, (ii) characterize the molecular mechanism of the migA/B DNA rearrangement, and (iii) assess the importance of the DNA rearrangement in chronic infection of hosts.

描述（改编自申请人的摘要）：铜绿假单胞菌，一种 机会致病菌，是导致死亡和死亡的主要病原体 免疫功能低下患者的发病率。 这也是最重要的 囊性纤维化患者的病原体。 在慢性感染期间， 已经确定了许多变化，包括压制特定的 毒力基因和表面变化。 为了鉴定毒力基因 金博士，铜绿假单胞菌在 CF 患者感染中起重要作用 开发了类似于体内表达技术的选择系统 首次描述于沙门氏菌。 使用这个系统，他识别出了三个 由 CF 气管支气管粘液诱导的遗传位点 患者。 这些基因座包括脓毒素受体、migA/B 基因座 与参与 LPS 合成的基因同源，并由 DNA 控制 重排开关，regA 是外毒素 A 合成的正调节因子。 在本申请中，金博士建议重点关注migA/B位点并进行测试 假设是 migA/B 基因座中的 DNA 重排造成的 慢性感染中观察到的 LPS 和外毒素 A 相变化。 实验旨在 (i) 定义 migA/B 基因的功能，(ii) 表征 migA/B DNA 重排的分子机制，以及 (iii) 评估 DNA 重排在慢性感染中的重要性 主机。