Haemophilus parainfluenzae and cardiopulmonary disease

性状（由申请方提供）：副流感嗜血杆菌是一种革兰氏阴性多形性杆菌，仅与人类宿主相关。多项临床报告显示，该细菌是革兰氏阴性菌感染性心内膜炎（IE）的最常见原因。感染性心内膜炎是一种细菌感染的心脏，通常涉及瓣膜。H.副流感病毒IE与高频率的脓毒性栓塞有关，其中包括细菌和血小板的植物性团块从主要感染部位脱落并通过血流传播。 虽然由革兰氏阴性菌引起的IE基本上未被研究，但对革兰氏阳性IE了解更多。这些研究表明，细菌与细胞外基质（ECM）组分结合的能力与细菌引起IE的能力之间存在很强的相关性。这与数据一致，数据显示，当心脏存在预先存在的损伤时，IE更为常见，导致损伤部位的ECM。细菌通过粘附ECM分子与心脏结合。然后粘附的细菌与血小板接触并结合它们。因此，细菌和宿主血小板的营养体开始扩张。如果这个植物体的一部分脱落，可能导致脓毒性栓塞。 本研究的具体目的是：1）表征H。副流感病毒与人ECM的结合并鉴定所涉及的分子;和2）表征H.副流感病毒对人血小板和相关分子的作用。为了实现这些目标，我们将利用H.使用细胞外基质成分和人血小板进行一系列粘附试验，检测副流感病毒。在对结合进行表征之后，将使用H.副流感最后，该小组已经确定了两个候选粘连，Haa和Hap。这些特定蛋白质在细菌粘附中的作用将被检查。 公共卫生相关性：副流感嗜血杆菌被认为是人类心肺系统的机会致病菌。特别是，它与感染性心内膜炎有关。本研究将探讨H.副流感病毒与细胞外基质和心脏瓣膜的组分以及Hia样粘附素蛋白Haa和Hap的结合。

DESCRIPTION (provided by applicant): Haemophilus parainfluenzae is a Gram-negative pleomorphic bacillus that is found exclusively associated with human hosts. Multiple clinical reports have shown the bacterium to be the most frequent cause of Gram-negative infective endocarditis (IE). Infective Endocarditis is a bacterial infection of the heart typically involving the valves. H. parainfluenzae IE has been associated with a high frequency of septic embolism in which vegetative masses, comprising bacteria and platelets, break off from the main site of infection and travel through the bloodstream. While IE caused by Gram-negative bacteria is essentially unstudied, more is known about Gram-positive IE. These studies have shown a strong correlation between the ability of the bacteria to bind to components of the extracellular matrix (ECM) and the ability of the bacteria to cause IE. This is consistent with data showing that IE is much more common when there is preexisting damage to the heart, resulting in ECM at the site of injury. The bacteria bind to the heart via adherence to ECM molecules. The adherent bacteria then come into contact with platelets and bind them. Thus, a vegetative body of bacteria and host platelets begin to expand. If part of this vegetative body breaks off, a septic embolism may result. The specific aims of this research are 1) to characterize the adherence of H. parainfluenzae to human ECM and to identify the molecules involved; and 2) to characterize the attachment of H. parainfluenzae to human platelets and the molecules involved. To accomplish these aims we will utilize wild type strains of H. parainfluenzae in a series of adherence assays using ECM components and human platelets. After characterization of the binding has been performed, identification of molecules involved will be done using a bank of random transposon insertion mutants of H. parainfluenzae. Finally, two candidate adhesions have already been identified by this group, Haa and Hap. The role of these specific proteins in bacterial adherence will be examined. PUBLIC HEALTH RELEVANCE: Haemophilus pararinfluenzae has been implicated as an opportunistic pathogen of the human cardiopulmonary system. In particular, it is has been implicated in infective endocarditis. The proposed research will examine the molecular mechanisms of adherence of H. parainfluenzae to components of the extracellular matrix and cardiac valves as well as Hia-like adhesin proteins Haa and Hap.