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核心分子机制。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衍生的分子决定因素。我们的研究表明，蜱宿主的立克次体感染也利用了与脊椎动物宿主细胞感染描述的类似过程。然而，立克次体蛋白在蜱感染中的作用尚不清楚。同样，尽管蜱对感染性立克次体做出积极反应，但协调蜱衍生反应的中心机制尚不清楚。因此，本申请的实验重点强调了立克次体感染背后的致病决定因素的作用以及介导载体成功定植的蜱免疫反应的细菌诱导的改变。以下具体目标将有助于更好地了解节肢动物媒介中立克次体感染和传播的成分。 1) 定义保守表面细胞抗原 (Sca) 对蜱载体 SFG 立克次体感染的贡献。已知 Sca 蛋白对于立克次体感染和脊椎动物细胞传播至关重要。我们假设有 将是与节肢动物载体感染相关的独特特征。此举的目的 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 立克次体的免疫反应与媒介能力的关系。蜱对 SFG 立克次体的强烈反应支持物种特异性宿主对立克次体感染的反应。因此，我们假设一个中心分子，Relish，负责立克次体成功定植和从节肢动物宿主清除之间的平衡。该目的的目的是描绘 IMD 免疫信号系统，重点关注蜱宿主中活性 Relish 的产生。

 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.