权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Evolution of chronic infection in Anasplasma phagocytophilum

嗜吞噬细胞无形体慢性感染的演变

基本信息

批准号：
7790602
负责人：
ANTHONY F. BARBET
金额：
$ 37.72万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-07-09 至 2012-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7790602
关键词：
Acute Agrobacterium Anaplasma Anaplasma phagocytophilum Animals Antigenic Diversity Antigens Bacteria Bartonella Behavior Biological Models Brucella Cell Communication Cells Chronic Chronic Disease Communicable Diseases Data Data Collection Disease Domestic Animals Ecosystem Ehrlichia Equus caballus Eukaryotic Cell Evaluation Evolution Generations Genetic Recombination Genome Genomics Goals Homologous Gene Human Immunity Immunodominant Antigens Individual Infection Invaded Kinetics Laboratories Lead Maintenance Mitochondria Modeling Molecular Natural Selections Organism Outcome Phylogenetic Analysis Plants Population Process Production Proteobacteria Pseudogenes Research Rickettsia Rodent Site Study models Surface Antigens Theoretical model Ticks Time Tropism Variant Vector-transmitted infectious disease base field study fitness genome sequencing man mathematical model pathogen pathogenic bacteria research study residence theories transmission process vector

项目摘要

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.

描述(申请人提供)：硬蜱传播的立克次体病原体吞噬细胞性无浆体和边缘立克次体可能导致人和动物的致命、急性或慢性疾病。这两种细菌的基因组都含有偶合基因；生物体通过将功能假基因重组成需要主要表面抗原的表达部位而与宿主免疫相互作用。这些生物是研究共同进化的有价值的模型，因为宿主施加的免疫导致的自然选择水平不同，通过扁虱和宿主传播施加的预定漂移，以及病原体利用的超重组策略。尽管有针对病原菌的最佳重组策略的理论，但特定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持久性的宿主、病媒和病原体之间的分子和进化相互作用来限制疾病的出现。其具体目的是：1.确定多种具有不同寄主嗜性的密切相关的吞噬弧菌菌株是否可能在自然生态系统中循环。2.对霍帕、WR和AP变异型1株吞噬弧菌的基因组进行测序。3.从实验上描述不同菌株在持续或有限感染的寄主物种中的感染动力学，以及4.模拟吞噬弧菌基因组种的进化和出现。其基本原理是，实地研究将记录共同进化的病原体-宿主物种关联；实验研究将展示水库宿主和感染限制宿主在通过免疫实施自然选择方面的不同；基因组研究将揭示细菌通过超重组表达表面抗原的物候在这些宿主中的不同；理论建模将整合实验室和现场收集的数据，以研究导致吞噬细胞巨噬菌感染发生和维持的共同进化、微生物和生态因素。最终，了解吞噬细胞菌-宿主相互作用中的进化因素和疾病机制将有助于我们控制病原菌引起的慢性感染，并提供限制这些疾病和其他媒介传播疾病的出现的管理方法。