Anaplasma marginale genes determining tick transmission

决定蜱传播的边缘无形体基因

• 批准号: 6899581
• 负责人: MICHAEL JAMES DARK
• 金额: $ 6.62万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6899581
• 关键词: Ixodes; Rickettsiales; arthropod borne communicable disease; bacteria infection mechanism; bacterial genetics; communicable disease transmission; comparative genomic hybridization; cow; disease vectors; juvenile animal

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.

描述（由申请人提供）：项目：立克次体目细菌导致人类和动物显著的发病率和死亡率。虽然立克次体的宿主范围各不相同，但都需要媒介进行传播。无形体属和埃里希体属，包括引起人类无形体病和人类埃里希体病的生物体，需要硬蜱媒介从哺乳动物宿主传播到易感宿主。这种传播需要病原体进入蜱的中肠，复制，迁移到唾液腺，并在传播前再次复制。这种发展在载体内的潜在机制代表了我们对立克次体发病机制的认识中的一个主要空白。 我建议使用比较基因组学方法，利用A。作为实验模型。对非传播性菌株进行测序并与先前测序的蜱传播性菌株进行比对将产生多态性列表。这些将在多种蜱虫传播菌株中进行检查，以消除与蜱虫传播性无关的差异，并产生候选基因列表。 将通过非传播性菌株的分子互补检测候选物是否参与蜱传播。 当成功完成后，这项研究将产生一个在A.边缘。比较相关的立克次体生物体将允许发现媒介入侵的共同机制，然后可以用于疾病控制策略。 候选人：候选人是一名兽医，完成了比较解剖病理学的住院医师和博士学位。℃下候选人已经完成了他的病理学培训沿着的大部分要求，以及所有的教学课程工作和他的候选人资格考试，并积极追求他的培训的研究部分。这一研究建议构成了他研究立克次体病原体媒介传播机制的计划。 工作环境：华盛顿州立大学的兽医微生物学和病理学系为传染病研究提供了现代化的研究设施，并提供了高度互动的培训环境，包括内部和跨学科的研究生教育，住院医生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进行独立研究。