Molecular Genetic Analysis of Chlamydia Pathogenicity

衣原体致病性的分子遗传学分析

• 批准号: 7336289
• 负责人: Anthony T Maurelli
• 金额: $ 28.86万
• 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 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7336289
• 关键词: Acute; Address; Animals; Bacteria; Biochemical; Biochemical Genetics; Biology; Blindness; Cellular biology; Cervicitis; Chlamydia; Chronic Disease; Communities; Complex; Coronary heart disease; DNA; Data; Development; Disease; Endocarditis; Epididymitis; Female; Genes; Genetic; Genetic Transformation; Goals; Growth; Infertility; Knowledge; Laboratories; Learning; Life Style; Maintenance; Methods; Methyltransferase; Molecular Genetics; Nonspecific urethritis; Organism; Pathogenesis; Pathogenicity; Pathway interactions; Pelvic Inflammatory Disease; Peptidoglycan; Pneumonia; Polyarthritides; Range; Research; Salpingitis; Sexually Transmitted Diseases; Source; System; Techniques; Work; cofactor; gene replacement; genetic analysis; interest; male; man; mutant; new technology; pathogen; success; tool; tool development; uptake; vaccine development

Bacteria of the genus Chlamydia are significant pathogens of animals and man. The diseases caused by Chlamydia spp. in man include pneumonia, 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. Chlamydia has also been implicated as a cofactor in a variety of chronic diseases such as coronary heart disease. 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 and expression of the foreign genes. Our long-term goal is to apply the power of genetics to study the pathogenic mechanisms of Chlamydia. The aims of this proposal include the development of genetic tools for the analysis of Chlamydia pathogenesis and hypothesis-driven aims to address specific questions of Chlamydia biology. The specific aims are to: 1) develop a method for introduction, expression, and stable maintenance of foreign DNA in Chlamydia and a system for gene replacement in Chlamydia; 2) characterize the pathway for peptidoglycan synthesis mChlamydia; and, 3) identify the transport system for uptake of essential constituents for Chlamydia growth, specifically the source of methyl donors for methyltransferases. We will employ genetic, biochemical and cell biology strategies to each aim. Success in achieving the first aim 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. Success in aim 2 will finally resolve the chlamydia anomaly while aim 3 will attempt to resolve another apparent paradox of Chlamydia biology. Thus, these two aims will resolve some long-standing questions of Chlamydia biology and extend our knowledge of the intracellular lifestyle of this important pathogen..

衣原体属细菌是动物和人类的重要病原体。引起的疾病有 衣原体属人类的疾病包括肺炎、心内膜炎、多关节炎、失明和多种 性传播疾病包括宫颈炎、输卵管炎、盆腔炎、不孕症等 女性；以及男性非淋菌性尿道炎和急性附睾炎。衣原体也受到牵连 作为冠心病等多种慢性疾病的辅助因子。尽管经过多年的努力， 由于其专性的细胞内生活方式和复杂性，衣原体仍然难以进行遗传分析 发育周期。没有人能够将外源DNA引入到这种生物体中并实现稳定 外源基因的遗传和表达。我们的长期目标是将遗传学的力量应用于 研究衣原体的致病机制。该提案的目标包括发展 用于分析衣原体发病机制的遗传工具和假设驱动的目标，以解决特定问题 衣原体生物学问题。具体目标是： 1）开发一种引入、表达、 衣原体中外源DNA的稳定维持以及衣原体基因替换系统； 2） 表征衣原体肽聚糖合成途径； 3) 确定运输系统 摄取衣原体生长的必需成分，特别是甲基供体的来源 甲基转移酶。我们将采用遗传、生化和细胞生物学策略来实现每个目标。成功于 实现第一个目标将对衣原体研究产生重大影响，为衣原体研究创造新工具 可获得衣原体的遗传分析。我们对衣原体发病机制了解的快速进展 和生物学以及构建用于疫苗开发的衣原体突变体的能力 通过这些新技术成为可能。目标 2 的成功将最终解决衣原体异常，而目标 3 的成功将最终解决衣原体异常问题 将尝试解决衣原体生物学的另一个明显的悖论。因此，这两个目标将解决 衣原体生物学的一些长期存在的问题并扩展我们对细胞内生活方式的了解 这种重要的病原体..