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

伯氏疏螺旋体（莱姆病的蜱传病原体）的群体基因组学

• 批准号: 9051058
• 负责人: Katharine Sassandra Walter
• 金额: $ 2.82万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-16 至 2017-12-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9051058
• 关键词: Area; Bacteria; Birds; Borrelia burgdorferi; Case Study; Communities; Data; Disease; Epidemic; Epidemiology; Evolution; Generations; Genes; Genetic; Genetic Structures; Genetic Variation; Genomics; Goals; Human; Hybrids; Knowledge; Lyme Disease; Mammals; Methods; Midwestern United States; Modeling; Molecular; North America; Order Spirochaetales; Outcome; Pathway interactions; Pattern; Phylogenetic Analysis; Population; Process; Public Health; Recording of previous events; Research; Research Design; Resolution; Resources; Risk; Route; Sampling; Single Nucleotide Polymorphism; Source; Structure; Surveys; System; Techniques; Ticks; United States; Vector-transmitted infectious disease; Virulence; base; cost effective; disorder control; field study; genome sequencing; genome-wide; genome-wide analysis; genomic variation; improved; next generation sequencing; novel; pathogen; predictive modeling; public health relevance; training opportunity; trait; whole genome

 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.

 描述（由申请人提供）：莱姆病细菌伯氏疏螺旋体（Bb）在美国的持续入侵带来了重大的公共卫生风险，也是研究持续病原体出现过程的独特机会。莱姆病是美国最流行的病媒传播疾病，并迅速从东北部和中西部的两个疫源地出现。尽管其流行病学的重要性，知识的来源和轨迹，目前的Bb入侵仍然是推测性的，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起源和途径，以预测进一步传播的区域，并改善疾病控制工作。系统地理学的方法使高分辨率的流行病学重要病原体的研究，包括强大的方法重建病原体入侵的历史和推断流行病的起源，入侵的路线，和空间传播的速度。此外，下一代测序（NGS）的进展使得在人群水平上产生全基因组序列（WGS）对于流行时间尺度上的病原体基因组变异的研究是高效且具有成本效益的。然而，NGS的力量和贝叶斯地理学的最新进展，尚未被利用的人口基因组研究的Bb，也没有调查的进化动力学Bb出现。这项研究旨在重建莱姆病螺旋体，伯氏疏螺旋体（Bb）的入侵历史，以更好地了解Bb出现的生态和环境驱动因素，并为预测病原体的持续传播提供信息。拟议的研究将（1）使用新的混合捕获方法直接从野外收集的蜱样本中获得Bb的WGS，并允许鉴定全基因组单核苷酸多态性（SNP），其将用于（2）在两个空间尺度上重建Bb出现的历史。拟议中的研究提供了一个重要的培训机会，在现场研究设计，病原体基因组学和地理分析。