Molecular basis for spotted fever group Rickettsia vector competence in ticks

 描述（由申请人提供）：立克次体是美国最严重的蜱传疾病之一的病原体。立克次体致病性和蜱传播途径（水平和垂直）的复合因素影响着人类立克次体病的生态学和流行病学。我们的长期目标是阐明蜱传播立克次体的分子机制。已经使用各种体外模型描述了脊椎动物细胞立克次体感染的细菌来源的分子决定因素。我们的研究表明，立克次体感染蜱宿主也利用类似的过程中描述的脊椎动物宿主细胞的感染。然而，立克次体蛋白在蜱感染中的作用尚不清楚。同样，尽管蜱虫对感染立克次体有积极的反应，但策划蜱虫反应的中枢机制尚不清楚。因此，本申请的实验重点强调立克次体感染的致病性决定因素和介导立克次体成功定殖载体的蜱免疫应答的细菌诱导的改变的作用。下面的具体目标将提供一个更好地了解立克次体感染和传播的节肢动物媒介的组成部分。1)确定保守的表面细胞抗原（Sca）对蜱虫载体SFG立克次体感染的贡献。已知Sca蛋白是立克次体在脊椎动物细胞中感染和传播所必需的。我们假设 将是与节肢动物媒介感染相关的独特特征。的目的 目的是确定立克次体蛋白在蜱宿主感染过程中的作用。2确定蜱对SFG立克次体的免疫应答如何与载体感受态相关。蜱对SFG立克次体的强烈反应支持了对立克次体感染的种特异性宿主反应。因此，我们推测，一个中央分子，调味剂，是负责成功的立克次体的殖民和清除节肢动物宿主之间的平衡。这个目标的目的是描绘IMD免疫信号传导系统，重点是在蜱宿主中产生活性Relish。

 DESCRIPTION (provided by applicant): Rickettsia rickettsii is the causative agent of one of the most severe tick-borne diseases in the United States. The compounding factors of rickettsial pathogenicity and route of tick transmission (horizontal and vertical) influence the ecology and epidemiology of human rickettsioses. Our long term goal is to elucidate the molecular mechanisms that are central to rickettsial transmission by ticks. The bacterial-derived molecular determinants of rickettsial infection of vertebrate cells have been described using various in vitr models. Our research indicates that rickettsial infection of tick hosts also utilizes similar processes described for infection of vertebrate host cells. However, the role of rickettsial proteins in tick infection is unknown. Likewise, although the tick actively responds to the infecting rickettsiae, the central mechanisms orchestrating the tick-derived response are not known. Thus, the experimental focus of this application emphasizes the roles of pathogenic determinants underlying rickettsial infection and the bacterial-induced alterations of the tick immune response mediating successful rickettsial colonization of the vector. The following specific aims will provide a better understanding of the constituents of rickettsial infection and transmission in arthropod vectors. 1) Defining the contribution of conserved surface cell antigens (Sca) to SFG Rickettsia infection of the tick vector. Sca proteins are known to be essential to rickettsial infection and dissemination in vertebrate cells. We hypothesize that there will be a distinct profile associated with infection of the arthropod vector. The objective of this aim is to define the role for rickettsial proteins during the infection process in the tick host. 2 To determine how the tick immune response to SFG Rickettsia correlates to vector competence. A vigorous tick response to SFG Rickettsia supports a species-specific host response to rickettsial infection. Therefore we hypothesize that a central molecule, Relish, is responsible for the balance between successful rickettsial colonization and clearance from the arthropod host. The objective of this aim is to delineate the IMD immune signaling system focusing on the production of active Relish in the tick host.