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，同时也为研究莱姆病病原体持续出现的过程提供了独特的机会。是美国最流行的媒介传播疾病，并且在东北部和中西部的两个疾病疫源地中迅速出现，尽管其流行病学重要性，但对当前 Bb 入侵的来源和轨迹的了解仍然是推测性的，仅限于。轶事病例报告和有限的昆虫学调查至关重要，以确定当前入侵的起源和途径，以预测进一步传播的地区并改进疾病控制工作，从而能够对流行病学上重要的病原体进行高分辨率研究。重建病原体入侵历史并推断流行病起源、入侵途径和空间传播速度的方法此外，下一代测序（NGS）的进步使得全基因组序列（WGS）的产生成为可能。然而，NGS 的力量和贝叶斯系统发育地理学的最新进展尚未用于 Bb 的群体基因组研究，也没有用于研究 Bb 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 (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，并为有关病原体持续传播的预测提供信息。拟议的研究将 (1) 使用新颖的混合捕获方法直接从现场收集的蜱样本中获得 Bb 的全基因组测序，并允许识别全基因组单核苷酸多态性 (SNP)，这将用于 (2) 重建 Bb 跨区域出现的历史拟议的研究为实地研究设计、病原体基因组学和系统地理学分析提供了重要的培训机会。