HOST CELL INTERACTIONS BY PATHOGENIC BORRELIAE

描述（改编自申请人的摘要）：伯氏疏螺旋体是 莱姆病的病原体，和B. hermsii和B.图里卡雷 蜱传回归热的病原体。病原体-宿主细胞相互作用 被认为是感染部位和严重程度的关键决定因素， Leong博士的研究小组专注于两类疏螺旋体的识别， 宿主细胞分子：（1）糖胺聚糖（GAG）;和（2）整联蛋白及其 相关蛋白质为了B。burgdorferi他们发现 GAG识别与宿主细胞类型特异性 结合，并确定了表面蛋白，Bgp，这可能是主要的B。 burgdorferiGAG受体这种细菌也能识别 活化依赖性血小板整合素α IIb β 3，从而选择性地 与活化的（与静息的）血小板结合。这种整合素结合活性是 预测将莱姆病螺旋体靶向血管壁， 血小板粘附，并可以解释莱姆病的一个显着特征： 动脉循环的血管病理学。 在梁博士对回归热螺旋体的研究中， 与血液中的高水平生长相关，并且变量主要 VspB蛋白促进与GAG的附着。另外，与B相反， burgdorferi，B. hermsii结合并激活静息血小板。血小板 活化活性显然是由整合素相关的 血小板信号分子CD 9。梁博士推测， 产生抗体反应，回归热螺旋体附着 直接通过GAG或间接通过活化和 粘附的血小板，可以减少细菌从 通过网状内皮系统控制血流。不断复制这些 粘附的细菌会导致高水平的细菌接种， 血流螺旋体与血小板的相互作用也可能有助于 血小板减少，是回归热的常见表现。

DESCRIPTION (Adapted from the Applicant's Abstract): Borrelia burgdorferi is the causative agent of Lyme disease, and B. hermsii and B. turicatae are causative agents of tick-borne relapsing fever. Pathogen-host cell interactions are thought to be critical determinants of the site and severity of infection, and Dr. Leong's group has focused on Borreliae recognition of two classes of host cell molecules: (1) glycosaminoglycans (GAGs); and (2) integrins and their associated proteins. For B. burgdorferi, they have found that differences in GAG recognition were associated with differences in host cell type-specific binding, and identified a surface protein, Bgp, that may be the major B. burgdorferi GAG receptor. This bacterium also recognizes the activation-dependent platelet integrin alphaIIbbeta3 and thereby selectively binds to activated (vs. resting) platelets. This integrin-binding activity is predicted to target the Lyme disease spirochete to the vessel wall at sites of platelet adherence, and could explain a salient feature of Lyme disease: vascular pathology of the arterial circulation. In Dr. Leong's studies of relapsing fever spirochetes, high-level GAG-binding correlated with high-level growth in the bloodstream, and a variable major protein, VspB, promoted attachment to GAGs. Additionally, in contrast to B. burgdorferi, B. hermsii bound and activated resting platelets. The platelet activation activity is apparently mediated by the integrin-associated platelet-signaling molecule CD9. Dr. Leong speculates that prior to the development of an antibody response, attachment of relapsing fever spirochetes to the vessel wall, either directly via GAGs or indirectly, via activated and adherent platelets, could diminish the clearance of bacteria from the bloodstream by the reticuloendothelial system. Continued replication by these adherent bacteria would result in high level bacterial seeding of the bloodstream. Interaction of spirochetes with platelets could also contribute to thrombocytopenia, a common manifestations of relapsing fever.