Doctoral Dissertation Research: Linking Population Genetics of Bacillus anthracis with Spatio-Temporal Patterns of Anthrax Outbreaks

了解炭疽病等疾病暴发的生态学以及景观生态学与特定细菌基因型之间的关联，对于改进野生动物、牲畜和人类的疾病预防和控制至关重要。炭疽病原体在细微的空间和时间尺度上传播的机制尚未得到很好的描述。这项博士论文研究项目将结合炭疽病原菌炭疽芽孢杆菌的分子分析和时空动物流行数据，探索不同时空尺度、多个遗传亚系和多个哺乳动物宿主系统的北美炭疽病动态。这位博士生将寻求以下问题的答案：来自受感染的动物宿主和尸食性苍蝇的炭疽杆菌潜在的进化变化是否表明病原体在局部范围内传播的机制？在不同生态环境和宿主系统的暴发中，生态条件、流行病学和遗传多样性之间是否存在关联？北美两个重要的炭疽疫源地炭疽杆菌遗传多样性的大范围时空模式是什么？学生将使用现有的炭疽杆菌分离株和来自生态不同地理区域的炭疽病家畜数据。将从研究期间发生的疫情中收集新的分离株和家畜数据。高分辨率单核苷酸重复(SNR)分析将表征研究地点之间和多个位点可变数目串联重复(MLVA)定义的基因型之间的遗传多样性。带有向量速度图的趋势面分析将被用来分析疾病在整个景观中通过宿主种群的传播，并将被基因型谱覆盖，以评估遗传多样性和疾病传播之间的关联。该项目将有助于填补关于炭疽传播的重要知识空白，并将专门评估遗传分析是否可以为炭疽传播的时空模型提供信息。炭疽的传播可能受到细微尺度的环境特征、遗传谱系、寄主种类和行为、节肢动物以及其他未知变量的影响。该项目将涵盖病原体的多个遗传谱系和多个宿主系统，包括德克萨斯州每年都有野生动物和野生动物/牲畜混合宿主种群的地方性炭疽病研究区域，以及蒙大拿州经历野生动物炭疽病重新出现的研究区域。项目结果将提供对一种重要溢出病原体的遗传多样性和进化的洞察。研究结果还将为预防野生动物、牲畜和人类疾病的公共卫生战略提供参考，并将为是否应针对当地生态制定战略提供见解。作为博士论文研究改进奖，该奖项还将提供支持，使有前途的学生建立一个强大的独立研究生涯。

Understanding the ecology of outbreaks of diseases like anthrax as well as associations between landscape ecology and specific bacterial genotypes is essential for improving prevention and control of the disease in wildlife, livestock, and humans. The mechanisms through which the anthrax pathogen is transmitted at fine spatial and temporal scales are poorly characterized. This doctoral dissertation research project will combine molecular analysis of Bacillus anthracis, the causative bacterium of anthrax, with spatio-temporal epizootic data to explore anthrax dynamics in North America across different spatial and temporal scales, multiple genetic sub-lineages, and multiple mammalian host systems. The doctoral student will seek answers to the following questions: Do potential evolutionary changes in B. anthracis from infected animal hosts and necrophagous flies suggest mechanisms of pathogen transmission at a local scale? Are there associations among ecological conditions, epidemiology, and genetic diversity within outbreaks in different ecological settings and host systems? What are the broad scale spatio-temporal patterns of genetic diversity of B. anthracis across two important anthrax foci in North America? The student will use an existing collection of B. anthracis isolates and anthrax epizootic data from ecologically distinct geographic areas. New isolates and epizootic data will be collected from outbreaks occurring during the study period. High-resolution single-nucleotide repeat (SNR) analysis will characterize genetic diversity among and within multiple locus variable number of tandem repeat- (MLVA) defined genotypes across study sites. Trend surface analysis with vector velocity mapping will be used to analyze disease movement through host populations across the landscape and will be overlain with maps of genotypes to evaluate associations between genetic diversity and disease transmission.This project will help fill important gaps in knowledge about anthrax transmission and will specifically evaluate whether genetic analysis can inform spatio-temporal models of anthrax transmission. Anthrax transmission is likely influenced by fine scale environmental characteristics, genetic lineage, host species and behaviors, and arthropods as well as other as-yet-unknown variables. This project will encompass multiple genetic lineages of the pathogen and multiple host systems, including a study area in Texas with annual, enzootic anthrax with wildlife and mixed wildlife/livestock host populations and a study area in Montana experiencing a reemergence of anthrax in wildlife. Project results will provide insight into the genetic diversity and evolution of an important spillover pathogen. The results also will inform public health strategies for prevention of wildlife, livestock, and human disease and will provide insight as to whether strategies should be tailored to the local ecology. As a Doctoral Dissertation Research Improvement award, this award also will provide support to enable a promising student to establish a strong independent research career.