Molecular basis for spotted fever group Rickettsia vector competence in ticks

 描述(申请人提供)：立克次体是美国最严重的壁虱传播疾病之一的病原体。立克次体致病性的复合因素和硬蜱传播途径(水平和垂直)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壁虱传播立克次体的核心分子机制。脊椎动物细胞中立克次体感染的细菌来源的分子决定因素已被用不同的IN-VITR模型描述。我们的研究表明，立克次体感染硬蜱宿主也采用了与脊椎动物宿主细胞感染类似的过程。然而，立克次体蛋白在硬蜱感染中的作用尚不清楚。同样，尽管壁虱对感染立克次体做出主动反应，但协调壁虱衍生反应的中心机制尚不清楚。因此，这一应用的实验重点强调了立克次体感染的致病决定因素的作用，以及细菌诱导的壁虱免疫反应的改变，介导了载体成功的立克次体定植。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)明确了保守的表面细胞抗原(SCA)在硬体立克次体感染中的作用。已知SCA蛋白是立克次体感染和在脊椎动物细胞中传播所必需的。我们假设在那里 将是一个与节肢动物媒介感染相关的明显特征。这样做的目的是 目的是确定立克次体蛋白在硬体宿主感染过程中的作用。2确定硬蜱对SFG立克次体的免疫应答与媒介能力之间的关系。对SFG立克次体的强烈扁虫反应支持对立克次体感染的物种特异性宿主反应。因此，我们假设，一个中心分子，味觉，负责在成功的立克次体定植和清除节肢动物宿主之间的平衡。这一目标的目的是描述IMD免疫信号系统，重点是在扁虱宿主中产生活跃的调味品。

 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.