DYNAMIC PLATELET - STAPHYLOCOCCAL INTERACTIONS

描述（来自申请人摘要的逐字描述）： 拟议的研究是全面表征分子间的相互作用， 金黄色葡萄球菌和血小板之间的动态剪切力的函数 为小说的发展提供理性的依据 治疗葡萄球菌性心血管感染。的假设 要测试的是，剪切应力会影响粘合剂之间的相互作用 血小板和S.（i）通过调节（i） 涉及的粘附分子和（ii）反应结合动力学。的 所提出的方法使用受控的、动态的、体外实验系统， 系统全面地研究血小板的重要性， 激活，血液成分，血流和细菌的发展， 血液传播的葡萄球菌感染这项工作的长期目标是 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： 全面阐明S.金色片晶 直接生理相关的剪切条件下的相互作用; 2） 描述S.细胞悬浮液中的金黄色-血小板异源聚集 控制剪切水平; 3）制定研究S. 目的：观察金葡菌对全血血小板聚集的影响， 在S.剪切条件下的金-血小板相互作用。完成 这些具体目标将为新的设计提供合理的基础。 治疗分子阻断特定的粘附事件，以及识别 疫苗开发中最重要的细菌受体。

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.