Anaplasma marginale genes determinning tick transmission

决定蜱传播的边缘无形体基因

• 批准号: 7082877
• 负责人: MICHAEL JAMES DARK
• 金额: $ 7.82万
• 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/7082877
• 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.

项目描述（由申请人提供）：立克次体目细菌在人类和动物中引起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，但都需要媒介传播。无形体病和埃利希体病属，包括导致人类无形体病和人类埃利希体病的生物，需要蜱虫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，并在传播之前再次复制。媒介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中的一个重大差距。