BIOLOGY OF PHAGE INFECTION IN CHLAMYDIA

描述(申请人提供)：人类的衣原体疾病包括主要的眼部、生殖器和呼吸道感染，后遗症包括失明、女性不孕、关节炎和哮喘。肺炎衣原体的慢性感染也与冠心病有关，冠心病是人类的头号杀手疾病。尽管衣原体在公共卫生中的规模很大，但作为临床医生和分子生物学家的传染病微生物，它们却以难以捉摸而闻名。这归因于几个因素，其中最突出的是一种独特的专属细胞内发育生活方式，以及衣原体至今仍抵抗基因操纵的事实。我们从鹦鹉热衣原体模型株？？豚鼠包涵性结膜炎？中分离到一个phiCPG1噬菌体。作为单链DNA小病毒科的成员，phiCPG1几乎 等同于？虚拟？通过基因组序列分析发现肺炎链球菌的噬菌体。细胞内病原体被自身寄生的噬菌体感染是一种独特的生物 这一现象对感染和疾病具有潜在的重要影响。此外，噬菌体为开发用于研究的分子和遗传工具提供了独特的机会。因此，这项应用的目的是在衣原体感染的背景下获得对衣原体噬菌体生物学的广泛了解。我们将确定噬菌体与宿主相互作用的分子基础，并比较评估无噬菌体和感染噬菌体细菌中的基因表达。在豚鼠身上建立良好的感染和疾病模型将使我们第一次能够研究噬菌体感染对脊椎动物由专性细胞内病原体自然感染的影响。最后，在这些研究中获得的信息将被用于开发衣原体的遗传方法。

DESCRIPTION (provided by applicant): Chlamydial disease of humans includes predominant ocular, genital and respiratory tract infections, with sequelae ranging from blindness, to female infertility, arthritis and asthma. Chronic infection with the respiratory pathogen, Chlamydia pneumoniae is also associated with coronary heart disease, the number one killer disease of humans. In spite of their public health magnitude, chlamydiae are reputed for their elusiveness as infectious microorganisms to clinicians and molecular biologists alike. This owes to several factors, prominent among which are a unique obligate intracellular developmental lifestyle and the fact that chlamydiae have resisted genetic manipulation to this day. We have isolated a bacteriophage, phiCPG1 from the model Chlamydia psittaci strain ?Guinea Pig Inclusion Conjunctivitis?. A member of the single-stranded DNA microviridae family, phiCPG1 is nearly identical to a ?virtual? phage of C. pneumoniae that was revealed by genome sequence analysis. The infection of an intracellular pathogen by its own parasitic bacteriophage is a unique biological phenomenon, with potentially important implications in infection and disease. Moreover, phages offer unique opportunities for the development of molecular and genetic tools for research. The objectives of this application are therefore to gain a broad understanding of Chlamydia phage biology in the context of chlamydial infection. We will determine the molecular basis of the interaction of the phage with its host and comparatively evaluate gene expression in phage-free and phage-infected bacteria. The availability of well-established models of infection and disease in the guinea pig will allow for the first time to study the impact of phage infection on the natural infection of a vertebrate animal by an obligate intracellular pathogen. Finally, the information gained in these studies will be exploited toward the development of genetic methodologies in Chlamydia.