Population genomics of Borrelia burgdorferi, the tick-borne agent of Lyme disease

 描述(由申请人提供)：莱姆病细菌伯氏疏螺旋体(BB)在美国的持续入侵构成了重大的公共卫生风险，也为研究持续病原体出现的过程提供了一个独特的机会。莱姆病是美国最流行的媒介传播疾病，正迅速从东北部和中西部的两个疫源地出现。尽管它在流行病学上很重要，但对当前BB入侵的来源和轨迹的了解仍然是推测的，仅限于轶事病例报告和有限的昆虫学调查。关键是要确定当前入侵的来源和途径，以便为进一步传播地区的预测提供信息，并改进疾病控制工作。系统地理学方法能够对流行病学上重要的病原体进行高分辨率研究，并包括重建病原体入侵历史和推断流行病来源、入侵途径和空间传播率的强大方法。此外，下一代测序(NGS)的进展使得在种群水平上产生全基因组序列(WGS)对于研究流行时间尺度上的病原体基因组变异具有效率和成本效益。然而，NGS的力量和贝叶斯系统地理学的最新进展，还没有被用于BB的种群基因组研究，也没有被用来研究BB出现的进化动力学。本研究旨在重建莱姆病螺旋体伯氏疏螺旋体的侵袭史，以更好地了解伯氏疏螺旋体出现的生态和环境驱动因素，并为病原体继续传播的预测提供依据。建议的研究将(1)使用新的杂交捕获方法直接从现场收集的扁虱样本中获得BB的WGS，并允许识别基因组范围的单核苷酸多态(SNPs)，这些SNPs将被用于(2)重建BB在两个空间尺度上的出现历史。拟议的研究在野外研究设计、病原体基因组学和系统地理分析方面提供了一个重要的培训机会。

 DESCRIPTION (provided by applicant): The ongoing invasion of the Lyme disease bacteria, Borrelia burgdorferi (Bb), in the United States presents a significant public health risk as well a a unique opportunity to study the process of ongoing pathogen emergence. Lyme disease is the most prevalent vector-borne disease in the USA and is rapidly emerging out of two disease foci in the Northeast and Midwest. Despite its epidemiological importance, knowledge of the source and trajectory of the current Bb invasion remains speculative, restricted to anecdotal case reports, and limited entomological surveys. It is critical to determine the origin and pathway of the current invasion to inform predictions about areas of further spread and improve disease control efforts. Phylogeographic approaches enable high-resolution study of epidemiologically important pathogens and include powerful methods for reconstructing the history of pathogen invasion and inferring epidemic origins, routes of invasion, and rates of spatial spread. Further, advances in next-generation sequencing (NGS) has made the generation of whole genome sequences (WGS) at the population-level efficient and cost-effective for study of pathogen genomic variation on epidemic timescales. However, the power of NGS and recent advances in Bayesian phylogeography, have not yet been harnessed for population genomic study of Bb, nor to investigate the evolutionary dynamics of Bb emergence. This study seeks to reconstruct the invasion history of the Lyme disease spirochete, Borrelia burgdorferi (Bb), to better understand the ecological and environmental drivers of Bb emergence and to inform predictions about continued pathogen spread. The proposed research will (1) use novel hybrid capture methods to obtain WGS of Bb directly from field- collected tick samples and allows identification of genome wide Single Nucleotide Polymorphisms (SNPs) that will be used to (2) reconstruct the history of Bb emergence across two spatial scales. The proposed research provides an important training opportunity in field study design, pathogen genomics, and phylogeographic analysis.