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

Arizona State University, Scottsdale AZ

Investigators

Abstract

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.