Doctoral Dissertation Research: The Zoonotic Origins of Tuberculosis Infection in the Pre-contact Americas

结核分枝杆菌在全球分布，每年感染100多万新患者。在接触前的美洲，结核病(TB)感染是由今天在海豹和海狮身上发现的一种菌株引起的。这个博士论文项目调查了一种人畜共患结核病菌株是如何适应人类作为主要宿主并在美洲传播的。在整个项目中，亚利桑那州立大学的本科生将接受基因组实验室工作和分析方面的培训，产生的数据集将用于创建本科生级别的研讨会。研究小组将通过促进关联方之间的相互理解和包容，从而促进机构之间的长期、创新和富有成效的关系，展示公平的国际合作。结核分枝杆菌复合体(MTBC)指的是一组导致人和动物感染结核病的类似病原体。从考古遗迹中提取的基因组表明，人畜共患病血统是过去人类感染结核病的原因。然而，今天人类中的大多数结核病感染是由结核分枝杆菌引起的，结核分枝杆菌是人类适应的MTBC血统。动物适应的病原体变成人类适应的病原体的进化步骤并不完全清楚。研究人员将对现代和古代的MTBC基因组进行比较，以更好地了解人畜共患结核病血统如何适应人类作为主要宿主。古代MTBC基因组将从考古骨骼中提取。研究小组将重点放在一个人口稠密的城市和贸易中心，以确定古代流通的MTBC菌株的基因组多样性的广度，其中一些可能是通过长途贸易进口的。随着人类人口的扩大和人与野生动物之间的界面变窄，了解人畜共患病传播动态的基因组基础将为公共卫生监测措施提供信息。这些比较的结果将有助于框架未来的流行病学、进化生物学和传染病研究。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Mycobacterium tuberculosis has a global distribution and infects over a million new people each year. In the pre-contact Americas, tuberculosis (TB) infection was caused by a strain that is found today in seals and sea lions. This doctoral dissertation project investigates how a zoonotic strain of TB adapted to humans as a primary host and spread across the Americas. Throughout the project, undergraduate students at Arizona State University will be trained in genomic lab work and analysis, and the resulting datasets will be used to create undergraduate-level workshops. The research team will demonstrate an equitable international collaboration by fostering mutual understanding and inclusivity among affiliated parties, thereby facilitating long-term, innovative, and productive relationships between institutions.The Mycobacterium tuberculosis complex (MTBC) refers to a group of similar pathogens that cause TB infection in humans and animals. Genomes extracted from archaeological remains show that zoonotic lineages were responsible for human TB infections in the past. Most TB infections in humans today, however, are caused by M. tuberculosis, the human-adapted MTBC lineage. The evolutionary steps of an animal-adapted pathogen becoming a human-adapted pathogen are not entirely understood. The researchers will draw comparisons between modern and ancient MTBC genomes to understand better how zoonotic lineages of TB adapt to humans as primary hosts. Ancient MTBC genomes will be extracted from archaeological skeletons. The research team focuses on a densely populated city and trade epicenter to determine the breadth of genomic diversity of ancient circulating MTBC strains, some of which were likely imported through long-distance trade. As human populations expand and the interface between humans and wildlife narrows, understanding the genomic underpinnings of zoonotic transmission dynamics will inform public health surveillance measures. The results of these comparisons will help frame future epidemiological, evolutionary biology, and infectious disease research.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.