Anaplasma marginale genes determining tick transmission

描述(申请人提供)：项目：立克次体菌目的细菌在人类和动物中会导致严重的发病率和死亡率。虽然立克次体的寄主范围各不相同，但都需要媒介传播。无浆体属和埃立克体属，包括引起人类无浆体病和埃立克体病的生物，需要硬蜱媒介才能从哺乳动物的宿主传播到敏感宿主。这种传播需要病原体进入扁虱的中肠，复制，迁移到唾液腺，并在传播之前再次复制。载体内这种发展的潜在机制代表了我们对立克次体发病机制的认识上的一个主要差距。 我建议使用比较基因组学的方法来研究这些途径，该方法以边际曲霉为实验模型。对非传播性毒株进行测序，并与之前测序的滴虫传播性毒株进行比对，将产生一份多态列表。这些基因将在多个壁虱传播的菌株中进行检查，以消除与壁虱传播性无关的差异，并产生候选基因清单。 候选人将通过非传播性毒株的分子互补来检测是否参与了壁虱的传播。当这项研究成功完成后，将产生一份在边缘黑线姬鼠中传播硬虱所必需的基因清单。对相关立克次体的比较将有助于发现媒介入侵的共同机制，然后可以利用这些机制制定疾病控制策略。 应聘者：应聘者是一名兽医，完成比较解剖病理学住院医师学位和博士学位。这位候选人已经完成了他的病理学培训的大部分要求，以及所有的教学课程工作和他的候选人资格考试，并正在积极地进行他的培训的研究部分。这项研究建议构成了他调查立克次体病原体媒介传播机制的计划。 环境：华盛顿州立大学兽医微生物学和病理学系为传染病研究提供现代化的研究设施和高度互动的培训环境，包括学科内和学科间的研究生教育、住院医师计划以及大学内外的广泛合作。赞助商在研究方面密切合作，并成功地指导临床医生、研究生和博士后研究员实现研究独立性。

DESCRIPTION (provided by applicant): The Project: Bacteria in the Order Rickettsiales cause significant morbidity and mortality in humans and animals. While the host range of the Rickettsiales varies, all require vectors for transmission. The genera Anaplasma and Ehriichia, including the organisms responsible for human anaplasmosis and human ehrlichiosis, require an ixodid tick vector for transmission from a mammalian reservoir to a susceptible host. This transmission requires the pathogen to enter the midgut of the tick, replicate, migrate to the salivary glands, and replicate again prior to transmission. The underlying mechanisms of this development within the vector represent a major gap in our knowledge of rickettsial pathogenesis. I propose to examine these pathways using a comparative genomic approach utilizing A. marginale as the experimental model. Sequencing of a non-transmissible strain and alignment with a previously sequenced tick transmissible strain will produce a list of polymorphisms. These will be examined in multiple tick-transmitted strains to eliminate differences not involved in tick transmissibility and produce a list of candidate genes. Candidates will be tested for involvement in tick transmission by molecular complementation of the nontransmissible strain. When successfully completed, this study will produce a list of genes necessary for tick transmission in A. marginale. Comparison of related rickettsial organisms will allow for discovery of common mechanisms of vector invasion, which can then be exploited for disease control strategies. The Candidate: The candidate is a veterinarian completing a residency in comparative anatomic pathology and a Ph.D. degree. The candidate has fulfilled most of the requirements of his pathology training along with all didactic course work and his candidacy exam, and is actively pursuing the research portion of his training. This research proposal constitutes his plan to investigate mecahnisms of vector transmission of rickettsial pathogens. Environment: The Department of Veterinary Microbiology and Pathology at Washington State University provides both modern research facilities for infectious disease research and a highly interactive training environment including intra- and interdisciplinary graduate education, residency programs, and extensive collaboration both within and ouside the university. The sponsors collaborate closely in research and have successfully mentored clinicians, graduate students, and post-doctoral fellows to research independence.