Evolution of chronic infection in Anasplasma phagocytophilum

描述（由申请方提供）：蜱传立克次体病原体嗜吞噬细胞无形体和A.边缘病可导致人和动物潜在的致命的急性或慢性疾病。两种细菌的基因组都含有偶然位点;生物体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中来与宿主免疫相互作用。这些生物体代表了有价值的模型，因为可变水平的自然选择，由于免疫施加的主机，专性漂移通过蜱和主机，和策略的超重组利用的病原体的传输。尽管致病菌的最佳重组策略的理论，具体的策略是高度可变的。很少有研究结合实验，现场，基因组和基于理论的研究，以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宿主、病媒和病原体之间导致持久性的分子和进化相互作用来限制疾病的出现。具体目标是：1.确定是否存在多株关系密切的A.嗜吞噬细胞菌具有不同的寄主嗜性，可在自然生态系统中循环。2.对Hoopa WR株和AP-1株的基因组进行测序。嗜吞噬细胞菌3.实验描述了不同菌株的感染动力学。在宿主物种中通常经历持续或有限感染的嗜吞噬细胞菌，和4.为了模拟A.嗜吞噬细胞菌基因种其基本原理是，实地研究将记录共同进化的病原体-宿主物种关系;实验研究将显示宿主和限制感染的宿主在通过免疫力实施自然选择方面的不同;基因组研究将揭示这些宿主中细菌通过超重组表达表面抗原的物候学如何不同;理论模型将整合实验室和现场收集的数据，以调查共同进化，微生物和生态因素的出现和维持。嗜吞噬细胞菌感染最终，了解A.嗜吞噬细胞-宿主相互作用和疾病机制的研究将有助于我们控制病原菌引起的慢性感染的能力，并提供限制这些和其他病媒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.