Genetic Determinants of Anaplasma Transmission

描述（由申请人提供）：研究计划：无形体属病原体（立克次体目）引起人类和动物疾病，包括人粒细胞埃立克体病（HGE），马埃立克体病，牛和羊无形体病。这些病原体是小的，革兰氏阴性的，专性细胞内细菌，需要蜱虫传播。蜱内的感染是在被感染哺乳动物的血液中开始的。然后无原体进入中肠上皮细胞，复制并移动到唾液腺。当受感染的蜱虫摄入第二顿血液时，细菌通过唾液分泌传播。重要的是，已经确定了嗜吞噬蜱和边缘蜱的蜱传性差异。HGE的发病率与细菌群体中遗传变异的数量之间存在很强的相关性，这表明只有某些嗜吞噬单胞杆菌基因型从宿主物种传播给人类。然而，蜱虫传播病原体的遗传决定因素尚不清楚，这表明我们在预防疾病暴发方面的知识存在重大差距。我建议研究可传播和不可传播的边缘无原体菌株作为模型，以确定无原体传播的分子决定因素。

DESCRIPTION (provided by applicant): Research Proposal: Pathogens within the genus Anaplasma (order Rickettsiales) cause human and animal diseases including human granulocytic ehrlichiosis (HGE), equine ehrlichiosis, and bovine and ovine anaplasmosis. These pathogens are small, Gram-negative, obligately intracellular bacteria that require ixodid ticks for transmission. Infection within the tick is initiated during a blood meal on an infected mammal. Anaplasma then enters the midgut epithelial cells, replicates, and moves to the salivary glands. The bacteria are transmitted via the salivary secretion when the infected tick ingests a second blood meal. Importantly, differences in the tick transmissibility of both A. phagocytophila and A. marginale have been identified. There is strong correlation between the incidence of HGE and the amount of genetic variation in the bacterial population suggesting that only certain A. phagocytophila genotypes are transmitted from the reservoir species to humans. However, the genetic determinants of pathogen transmissibility by ticks are unknown, representing a significant gap in our knowledge relevant to prevention of disease outbreaks. I propose to study transmissible and non-transmissible strains of Anaplasma marginale as a model to identify the molecular determinants of Anaplasma spp. transmission. The Candidate: The candidate is a veterinarian with two years of experience in clinical practice, including an internship, and will complete her 3 year residency in anatomic pathology in June 2002. In preparation for research raining, the candidate has completed the didactic course work for the PhD and passed the doctoral preliminary examination. The research proposed in this document constitutes her plan to complete doctoral research focusing on vector borne and emergent disease. Environment: The Department of Veterinary Microbiology and Pathology provides both modern research facilities for infectious disease research and a highly interactive training environment including intra- and interdisciplinary graduate education and extensive collaboration both within and the outside the university. The sponsor has an active research program in vector borne disease has successfully mentored clinicians, graduate students, and post-doctoral fellows to research independence.