H. influenzae genes associated with COPD

描述（由申请人提供）： 项目概要：慢性阻塞性肺疾病是环境因素、宿主免疫反应和微生物因素复杂相互作用的结果。流感嗜血杆菌（Haemophilus influenzae）细菌定植于人类呼吸道，并且是与COPD相关的重要病原体。本研究的总体目标是确定H。流感因子是导致COPD发病的重要因素。在这个建议中利用的基本原则是H。流感在遗传上是高度可变的，自然选择保留了特定细菌群体中的必要基因。在特定目标1中，已知H.流感病毒毒力基因将在H.从COPD患者和非COPD成人中分离的流感病毒株。在Specific Aim 2中，在H.将鉴定从COPD患者和非COPD成人中分离的流感病毒。这项基因发现工作将利用消减基因组杂交来鉴定H。流感病毒DNA片段，其对应于代表性COPD H中存在的基因。流感病毒株，但在代表性流感病毒株中不存在。COPD和非COPD患者中产生的DNA片段的患病率。将使用细菌基因组微阵列技术评估流感菌株。此外，COPD相关DNA片段的相应基因也将在H.流感病毒染色体的缺失，并在评估的Escherosal菌株的侧翼区域中的缺失程度。在具体目标3中，将描述COPD菌株中潜在COPD相关毒力基因的共存，并使用分类树分析确定每个基因对“COPD致病型”的相对贡献。在具体目标4中，研究了人上皮细胞对H.将使用ELISA测量“COPD病理型”的流感。项目相关性：本项目的结果将确定H。与COPD相关的流感病毒基因将描述它们在刺激人类上皮细胞的免疫应答中的作用。这些结果将有助于更好地了解H。流感病毒毒力途径与COPD相关，并导致预防和管理COPD的新的新策略。(End摘要）

DESCRIPTION (provided by applicant): PROJECT SUMMARY: Chronic obstructive pulmonary disease results from a complex interplay of environmental factors, host immune responses, and microbial factors. The bacterium Haemophilus influenzae colonizes the human respiratory tract and is an important pathogen associated with COPD. The overall goal of this study is to identify H. influenzae factors that contribute to the pathogenesis of COPD. The underlying principles exploited in this proposal are that H. influenzae are genetically highly variable and that natural selection preserves necessary genes among specific populations of bacteria. In Specific Aim 1 the prevalence of known H. influenzae virulence genes will be described among H. influenzae strains isolated from patients with COPD and from adults without COPD. In Specific Aim 2 additional genes that segregate differentially among H. influenzae isolated from patients with COPD and from adults without COPD will be identified. This gene discovery effort will utilize subtractive genomic hybridization to identify H. influenzae DNA fragments that correspond to genes present in a representative COPD H. influenzae strain but absent in a representative commensal strain. The prevalence of the resultant DNA fragments among COPD and non-COPD H. influenzae strains will be assessed using a bacterial genomic microarray technique. In addition, the corresponding genes of the COPD-associated DNA fragments will be defined and mapped on the H. influenzae chromosome, and the extent of the deletion in flanking regions of the commensal strain assessed. In Specific Aim 3, the co-occurrence of the potential COPD-associated virulence genes among COPD strains will be described and the relative contribution of each gene to the "COPD pathotype" will be determined using a classification tree analysis. In Specific Aim 4, the expression of immune mediators by human epithelial cells in response to H. influenzae of the "COPD pathotypes" will be measured using ELISA. PROJECT RELEVANCE: The results of this project will identify H. influenzae genes that are associated with COPD will describe their role in stimulating immune responses by human epithelial cells. These results will lead to a better understanding of the H. influenzae virulence pathways associated with COPD and lead to novel new strategies for prevention and management of COPD. (End of Abstract)