Spread of Lyme borreliosis bacteria in the U.S.

描述（由申请人提供）：美国莱姆病的新发人类病例数量最近跃升至历史新高，表明狭义伯氏疏螺旋体（s.s.）正在加速膨胀本申请的广泛和长期目标是解开作用于细菌的进化过程，以便于模拟B的致病基因型的传播。狭义伯氏疏在美国，并提供理论基础，开发新的诊断工具和设计具体的控制方法莱姆病。因此，迫切需要建立一个B的多位点序列分型（MLST）方案。狭义伯氏疏基于管家基因，以分析在美国致病基因型的最近的人口增长，范围扩展和人口动态。具体目标是：（一）建立一个B的最低限度标准培训计划。狭义伯氏疏基于管家基因，（ii）评估野生型B的现今遗传群体结构。狭义伯氏疏人口在美国东北部使用MLST和景观遗传学，及（iii）推断最近的人口模式的B。burgdorferi s.s.，例如人口瓶颈和人口扩张。B的分离株。狭义伯氏疏将在整个新英格兰的不同地理范围内对来自探索蜱的样本进行采样，并通过MLST进行基因分型。使用一种新的算法（eBURST），将阐明细菌种群之间的进化下降模式。疏螺旋体种群的空间结构将由空间统计确定，并与景观变量相关。利用地理信息系统，将产生一个综合地图，显示内插遗传表面。将估计形成细菌种群的进化过程的相对重要性，如突变、重组、迁移和选择。MLST在管家基因和景观遗传学的野生型疏螺旋体种群的分析是新颖的和探索性的，并可能在我们的理解新出现的媒介传播的人畜共患病病原体的演变开辟新的天地。

DESCRIPTION (provided by applicant): The number of new human cases of Lyme borreliosis in the United States has recently leaped to record highs, suggesting that the populations of the disease-causing genotypes of Borrelia burgdorferi sensu stricto (s.s.) are expanding at an accelerating rate. The broad and long-term objectives of this application are to disentangle the evolutionary processes acting on the bacteria to facilitate modelling the spread of disease-causing genotypes of B. burgdorferi s.s. in the United States, and to provide rationales for developing new diagnostic tools and for designing specific control methods of Lyme borreliosis. There is urgent need to establish a Multilocus Sequence Typing (MLST) scheme for B. burgdorferi s.s. based on housekeeping genes in order to analyze the recent population growth, range expansion and population dynamics of pathogenic genotypes in the United States. The specific aims are (i) to establish a MLST scheme of B. burgdorferi s.s. based on housekeeping genes, (ii) to assess the present day genetic population structures of wild-type B. burgdorferi s.s. populations in the Northeast United States using MLST and landscape genetics, and (iii) to infer the recent demographic patterns of B. burgdorferi s.s., such as population bottlenecks and expansions. Isolates of B. burgdorferi s.s. derived from questing ticks will be sampled at different geographical scales across New England and will be genotyped by MLST. Using a new algorithm (eBURST), the patterns of evolutionary descent amongst the bacterial populations will be clarified. The spatial structure of the Borrelia populations will be determined by spatial statistics and related to landscape variables. Using GIS, a synthesis map will be generated that displays an interpolated genetic surface. The relative importance of the evolutionary processes that have been shaping the bacterial populations, such as mutation, recombination, migration and selection, will be estimated. The analyses of wild-type Borrelia populations by MLST at housekeeping genes and by landscape genetics is novel and explorative, and could break new ground in our understanding of the evolution of emerging vector-borne zoonotic pathogens.