DYNAMIC PLATELET - STAPHYLOCOCCAL INTERACTIONS

描述(逐字摘自申请者摘要)： 建议的研究是全面描述分子间的相互作用。 动态剪切作用下金黄色葡萄球菌与血小板之间的关系 以期为小说的发展提供理性的依据 对抗葡萄球菌心血管感染的治疗。假说 有待检验的是，剪切力影响粘结剂之间的相互作用 通过调节血小板和金黄色葡萄球菌的相对重要性 粘合分子的参与；(Ii)反应结合动力学。这个 建议的方法使用受控的、动态的、体外实验系统 系统、全面地审视血小板的重要性 激活、血液成分、血液流动和细菌在发展中的作用 血源性葡萄球菌感染。这项工作的一个长期目标是 探讨血栓形成与心血管疾病的相互关系 感染机制。该项目的具体目标是：1) 全面阐明金黄色葡萄球菌-血小板的分子机制 直接生理相关的剪切条件下的相互作用；2) 金黄色葡萄球菌细胞悬液中金黄色葡萄球菌-血小板异质性聚集的特征 以控制剪切水平；3)制定研究S。 全血中金-血小板聚集及其影响因素的研究 剪切条件下金黄色葡萄球菌与血小板相互作用的扩展。完成 这些具体目标将为新建筑的设计提供合理的依据 治疗分子，以阻断特定的粘连事件，以及识别 疫苗开发中最重要的靶向细菌受体。

DESCRIPTION (Verbatim from Applicant's Abstract): The broad objective of the proposed research is to comprehensively characterize the molecular interactions between Staphylococcus aureus and platelets as a function of the dynamic shear environment in order to provide a rational basis for the development of novel treatments to combat staphylococcal cardiovascular infections. The hypothesis to be tested is that shear stress affects the adhesive interactions between platelets and S. aureus by modulating the (i) relative importance of the adhesive molecules involved and (ii) the reaction binding kinetics. The proposed approach uses controlled, dynamic, in vitro experimental systems to systematically and comprehensively examine the importance of platelet activation, blood components, blood flow, and bacteria in the development of blood-born staphylococcal infections. A long-term goal of this work is to investigate the interrelationship between thrombogenesis and cardiovascular infection mechanisms. The specific aims of the project are to: 1) comprehensively elucidate the molecular mechanisms of S. aureus-platelet interactions under shear conditions of direct physiological relevance; 2) characterize S. aureus-platelet heteroaggregation in cell suspensions subjected to controlled levels of shear and; 3) develop a protocol to study S. aureus-platelet aggregation in whole blood and to evaluate the effect of this extension on S. aureus-platelet interactions under shear conditions. Completion of these specific aims will provide a rational basis for the design of new therapeutic molecules to block specific adhesion events, as well as identify the most important bacterial receptors to target in vaccine development.