MOLECULAR GENETIC ANALYSIS OF CHLAMYDIA PATHOGENICITY

衣原体致病性的分子遗传学分析

• 批准号: 2728334
• 负责人: Anthony T Maurelli
• 金额: $ 26.1万
• 依托单位: HENRY M. JACKSON FDN FOR THE ADV MIL/MED
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 2003-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2728334
• 关键词: Chlamydiaceae; bacterial DNA; bacterial cytopathogenic effect; bacterial genetics; genetic manipulation; genetic techniques; molecular cloning; molecular genetics; mutant; phenotype; plasmids; technology /technique development; transposon /insertion element

DESCRIPTION (Adapted from the Applicant's Abstract): Bacteria of the genus Chlamydia are significant pathogens of animals and man. The diseases caused by Chlamydia spp. in man include pneumonitis, endocarditis, polyarthritis, blindness, and a wide range of sexually transmitted diseases including cervicitis, salpingitis, pelvic inflammatory disease, and infertility in females; and non-gonococcal urethritis and acute epididymitis in males. Despite many years of effort, the Chlamydia remain intractable to genetic analysis due to their obligate intracellular lifestyle and complex developmental cycle. No one has been able to introduce foreign DNA into this organism and achieve stable inheritance of the expression of the foreign genes. Few attempts at isolation of Chlamydia mutants have been reported. Even cloning of Chlamydia genes by complementation has been problematic due to the absence of, or poor expression of cloned Chlamydia genes in Escherichia coli. Our long term goal is to apply the power of genetics to study the pathogenic mechanisms of Chlamydia. The goal of this proposal is to develop genetic tools for the analysis of Chlamydia biology and pathogenesis and to use these tools to address specific problems of Chlamydia pathogenesis. The Specific aims are to: 1) design an efficient, reproducible method for introduction, expression, and stable maintenance of foreign DNA in Chlamydia; 2) design genetic tools for mutagenesis and selection of mutant phenotypes of Chlamydia ; 3) clone Chlamydia genes by functional complementation; and, 4) develop a system for gene replacement in Chlamydia. Each of these aims will include development of a genetic tool, demonstration of the tools effectiveness, and application of the tool to a fundamental question of Chlamydia biology. Success in achieving these goals will have a significant impact on Chlamydia research by making new tools for genetic analysis of Chlamydia available. Rapid advances in our understanding of Chlamydia pathogenesis and biology as well as the ability to construct Chlamydia mutants for vaccine development will be made possible by these new techniques.

描述（改编自申请人的摘要）： 衣原体是动物和人的重要病原体。这 衣原体属引起的疾病。人包括肺炎， 心内膜炎，多重关节炎，失明和广泛的性行为 传播疾病，包括宫颈炎，盐炎，骨盆 女性炎症性疾病和不育症；和非群球菌 男性尿道炎和急性附加炎。尽管多年 努力，由于 他们的义务细胞内生活方式和复杂的发展周期。 没有人能够将外国DNA引入该生物体， 实现外国基因表达的稳定遗传。很少 据报道，已经尝试隔离衣原体突变体。甚至 通过互补克隆衣原体基因的克隆是有问题的 在缺乏克隆衣原体基因的表达或不良表达 大肠杆菌。我们的长期目标是运用遗传学的力量 研究衣原体的致病机制。目标的目标 建议是开发遗传工具来分析衣原体 生物学和发病机理，并使用这些工具来解决特定 衣原体发病机理的问题。具体目的是：1）设计 一种有效的，可再现的方法，用于引入，表达和 在衣原体中稳定维护外国DNA； 2）设计遗传工具 用于衣原体突变表型的诱变和选择； 3） 克隆衣原体基因通过功能互补；以及，4）开发一个 衣原体中基因置换的系统。这些目标将 包括开发遗传工具，演示工具 有效性以及该工具将工具应用于一个基本问题 衣原体生物学。实现这些目标的成功将有一个 通过为遗传制造新工具对衣原体研究的重大影响 可用的衣原体分析。我们对理解的快速发展 衣原体的发病机理和生物学以及构建能力 这些因疫苗开发的衣原体突变体将使这些突变体成为可能 新技术。