Vascular Molecular Pathogenesis of Chlamydia pneumoniae

肺炎衣原体的血管分子发病机制

• 批准号: 6792645
• 负责人: Gerald Irwin Byrne
• 金额: $ 35.49万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6792645
• 关键词: Chlamydiaceae; atherosclerosis; bacterial genetics; chlamydial disease; clinical research; gene expression profiling; genetic polymorphism; genetic strain; genotype; host organism interaction; human subject; microorganism culture; microorganism growth; molecular pathology; virulence

DESCRIPTION (provided by the applicant): Chlamydia pneumoniae infection is associated with atherosclerosis progression, destabilization of atherosclerotic lesions, and cardiovascular disease yet our understanding of how this organism may causally contribute to chronic diseases is not well understood. C. pneumoniae is an obligate intracellular prokaryotic bacterial pathogen that can modulate its interaction with host cells to produce either acute productive infection or chronic persistent infection. Isolates of C. pneumoniae exhibit a finite number of genomic polymorphisms suggesting that intra-strain heterogeneity reflect variants suited for growth or persistence in different in vivo environments or host cell types. We propose to compare respiratory and cardiac C. pneumoniae isolates, plaque, clone and analyze individual variants by polynucleotide polymorphism analysis to identify different genotypes that may be present within single strains or selected in different in vivo environments. We will then test these genotypes in models of in vitro infection to identify strains with propensities to cause chronic infection and atherosclerotic disease. Molecular genetic analysis of the growth of these genotypes using microarray gene expression profiling and quantitative real time polymerase chain reaction will identify subsets of genes that are predictive of acute and chronic diseases. These objectives will be accomplished according to two specific aims involving (1) plaquing, cloning and analyzing chlamydial variants obtained from respiratory and cardiovascular sites and, (2) molecular analysis of pathogen and host cell gene usage patterns during differing growth conditions. These investigations will provide useful information on the degree of genetic heterogeneity inherent in C. pneumoniae populations and how this heterogeneity may contribute to the pathogenesis of C. pneumoniae disease. Results also will have the practical application of providing information to obtain the identity of subsets of C. pneumoniae genes or their products that can be used to target the development of new diagnostic tools or intervention strategies to populations that are at risk of heart disease with a C. pneumoniae-mediated component and to the identification of chronic chlamydial infections in general.

描述（由申请人提供）： 肺炎衣原体感染与动脉粥样硬化进展、动脉粥样硬化病变不稳定和心血管疾病有关，但我们对这种生物体如何导致慢性疾病的了解尚不清楚。肺炎衣原体是一种专性细胞内原核细菌病原体，可以调节其与宿主细胞的相互作用，产生急性生产性感染或慢性持续性感染。 肺炎衣原体分离株表现出有限数量的基因组多态性，表明菌株内异质性反映了适合在不同体内环境或宿主细胞类型中生长或持续存在的变异体。 我们建议通过多核苷酸多态性分析来比较呼吸道和心脏肺炎衣原体分离株、斑块、克隆和分析个体变体，以鉴定可能存在于单一菌株中或在不同体内环境中选择的不同基因型。 然后，我们将在体外感染模型中测试这些基因型，以确定具有引起慢性感染和动脉粥样硬化疾病倾向的菌株。 使用微阵列基因表达谱和定量实时聚合酶链反应对这些基因型的生长进行分子遗传学分析，将鉴定出可预测急性和慢性疾病的基因子集。 这些目标将根据两个具体目标来实现，包括（1）从呼吸和心血管部位获得的衣原体变体的斑块、克隆和分析，以及（2）不同生长条件下病原体和宿主细胞基因使用模式的分子分析。 这些研究将为肺炎衣原体种群固有的遗传异质性程度以及这种异质性如何影响肺炎衣原体疾病的发病机制提供有用的信息。 研究结果还将具有实际应用价值，即提供信息来鉴定肺炎衣原体基因或其产物的子集，这些信息可用于针对有心脏病风险的人群开发新的诊断工具或干预策略。肺炎衣原体介导的成分和慢性衣原体感染的一般鉴定。