Evolution of chronic infection in Anasplasma phagocytophilum

描述（由申请人提供）：蜱传播的立克次体病原体嗜吞噬细胞无原体和边缘无原体可引起人类和动物的急性或慢性致命疾病。这两种细菌的基因组都含有偶然性位点；这些生物通过将功能性假基因重组到需要主要表面抗原的表达位点来与宿主免疫相互作用。由于宿主施加的免疫、蜱虫和宿主传播施加的专性漂移以及病原体利用的超重组策略，这些生物代表了研究共同进化的有价值的模型。尽管理论对病原菌的最佳重组策略，具体的策略是高度可变的。很少有研究结合实验、实地、基因组和基于理论的研究来调查新的慢性传染病的演变和出现。我们的长期目标是通过研究导致疾病持续存在的宿主、媒介和病原体之间的分子和进化相互作用来限制疾病的出现。具体目标是：1。目的：确定多种亲缘关系密切的嗜吞噬单胞菌是否可能在自然生态系统中循环。2. 目的：测定嗜吞噬细胞芽孢杆菌Hoopa WR和ap -变异1株的基因组序列。3. 3 .实验描述不同菌株在宿主物种中持续或有限感染的吞噬细胞芽胞杆菌感染动力学；模拟嗜吞噬细胞芽孢杆菌基因种的进化和出现。理由是实地研究将记录共同进化的病原体-宿主物种关联；实验研究将显示宿主和限制感染宿主在通过免疫施加自然选择方面的差异；基因组研究将揭示细菌通过超重组表达表面抗原在这些宿主中的物候差异；理论建模将整合实验室和实地收集的数据，以研究嗜吞噬芽胞杆菌感染出现和维持的共同进化、微生物和生态因素。最终，了解A.吞噬细胞-宿主相互作用的进化因素和疾病机制将有助于我们控制由致病菌引起的慢性感染的能力，并提供限制这些和其他媒介传播疾病出现的管理方法。

DESCRIPTION (provided by applicant): The tick-transmitted rickettsial pathogens Anaplasma phagocytophilum and A. marginale cause potentially fatal, acute or chronic disease of man and animals. The genomes of both bacteria contain contingency loci; the organisms interact with host immunity by recombination of functional pseudogenes into expression sites needing major surface antigens. These organisms represent valuable models for the study of coevolution because of variable levels of natural selection due to immunity imposed by hosts, obligate drift imposed by transmission through ticks and hosts, and strategies of hyper-recombination utilized by the pathogens. Despite theories of optimal recombination strategies for pathogenic bacteria, particular strategies are highly variable. Few studies have combined experimental, field, genomic, and theory-based research to investigate the evolution and emergence of new chronic infectious disease. Our long-term goals are to limit disease emergence through a study of molecular and evolutionary interactions between hosts, vectors and pathogens that lead to persistence. The specific aims are: 1. To determine if multiple closely-related strains of A. phagocytophilum with different host tropisms may circulate in natural ecosystems. 2. To sequence the genomes of the Hoopa WR and AP-variant 1 strains of A. phagocytophilum. 3. To experimentally describe the kinetics of infection by different strains of A. phagocytophilum in host species that typically undergoes persistent or limited infections, and 4. To model the evolution and emergence of A. phagocytophilum genospecies. The rationale is that field studies will document coevolved pathogen-host species associations; experimental research will show how reservoir and infection-limiting hosts differ in their imposition of natural selection via immunity; genome studies will reveal how the phenology of bacterial expression of surface antigens through hyper-recombination differs in these hosts; and theoretical modeling will integrate laboratory and field-collected data to investigate coevolutionary, microbiological, and ecological factors underlying the emergence and maintenance of A. phagocytophilum infection. Ultimately, understanding evolutionary factors in A. phagocytophilum-host interactions and disease mechanisms will contribute to our ability to control chronic infections caused by pathogenic bacteria and provide management approaches that limit the emergence of these and other vector-borne diseases.