BIOLOGY OF PHAGE INFECTION IN CHLAMYDIA

描述（由申请方提供）：人类衣原体疾病主要包括眼部、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。慢性感染呼吸道病原体，肺炎衣原体也与冠状动脉心脏病，头号杀手疾病的人类。尽管衣原体在公共卫生方面的重要性，但对于临床医生和分子生物学家来说，它们作为传染性微生物的隐匿性是众所周知的。这归因于几个因素，其中突出的是一个独特的专性细胞内发育的生活方式和事实，衣原体抵制遗传操纵到今天。 我们从鹦鹉热衣原体的模型菌株中分离到了噬菌体phiCPG1。豚鼠包涵体结膜炎？。作为单链DNA微病毒科的一员，phiCPG1几乎是 与A相同？虚拟？噬菌体C. pneumoniae的基因组序列分析显示。细胞内病原体被其自身的寄生噬菌体感染是一种独特的生物学过程， 这种现象在感染和疾病中具有潜在的重要意义。此外，生物多样性公约为开发分子和遗传研究工具提供了独特的机会。因此，本申请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理解。我们将确定噬菌体与其宿主相互作用的分子基础，并比较评估无噬菌体和噬菌体感染的细菌中的基因表达。在豚鼠中建立良好的感染和疾病模型的可用性将允许第一次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利用对衣原体的遗传方法的发展。

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.