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（申请人提供）： 肺炎衣原体感染与动脉粥样硬化的进展，动脉粥样硬化病变的不稳定和心血管疾病有关，但我们对这种生物可能如何对慢性疾病有效的理解却尚未得到充分了解。肺炎梭菌是一种强制性细胞内核细菌病原体，可以调节其与宿主细胞的相互作用，以产生急性生产感染或慢性持续感染。 肺炎梭状芽胞杆菌的分离株表现出有限数量的基因组多态性，这表明施加内链异质性反映了适用于体内环境或宿主细胞类型中不同生长或持久性的变异。 我们建议通过多核苷酸多态性分析比较呼吸和心脏梭菌分离株，斑块，克隆，并分析单个变体，以鉴定单个菌株中可能存在或在不同的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，以鉴定具有倾向的菌株，以引起慢性感染和动脉粥样硬化疾病。 使用微阵列基因表达分析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分析将鉴定可预测急性和慢性疾病的基因子集。 这些目标将根据涉及（1）从呼吸道和心血管部位获得的斑块，克隆和分析的两个特定目的来实现，（2）在不同生长条件下的病原体和宿主细胞基因使用模式的分子分析。 这些研究将提供有关肺炎梭菌种群固有的遗传异质性程度的有用信息，以及该异质性如何有助于肺炎梭菌疾病的发病机理。 结果还将具有提供信息的实际应用，以获得肺炎梭状芽胞杆菌基因的亚群或其产品的标识，可用于针对新的诊断工具或干预策略的开发，以对患有心脏病风险的人群伴有肺炎梭菌介导的成分以及一般慢性疫苗感染的识别。