NSF EEID Project - French Guiana

Understanding and controlling emerging infectious diseases before they reach epidemic proportions is important for preventing devastating effects on human health, promoting animal welfare, and improving species conservation. Buruli ulcer disease is a chronic, debilitating infection that destroys skin, soft tissues, and bone, and has been reported from over 30 countries worldwide. Disease is caused by Mycobacterium ulcerans, a pathogen closely related to those that cause tuberculosis and leprosy. Multiple mechanisms by which humans get M. ulcerans have been proposed but there is uncertainty in identifying ecological reservoirs for replication and mechanisms that allow it to persist and disperse in the environment. This project tests how M. ulcerans has evolved to produce a novel molecular weapon that allows it to persist and disperse in environments where human contact is at highest risk. This molecular weapon is the toxin responsible for Buruli ulcer. Furthermore, communities of microbes (microbiomes) associated with hosts constantly interact with potential pathogens. This project examines how an environmental pathogen persists and replicates among host and environmental microbiomes. Discovering new interactions between disease-causing organisms and their environment provides insight into the basic understanding of how diseases emerge and spread. This interdisciplinary project will train undergraduates, graduate students, and research professionals with focused inclusion of diverse individuals from underrepresented groups, military veterans, and indigenous cultures. In addition, this work will contribute publicly available data that can be used by other researchers and public health professionals to deliver educational tools necessary to improve broader health outcomes.

The research will test a Novel Weapons Hypothesis using a mycobacterial clade that demonstrates diversity of genes that produces mycolactone, the toxin responsible for Buruli ulcer. Mycolactone is hypothesized to have initially evolved to facilitate mycobacterial colonization and persistence in complex microbial consortia of environmental hosts and reservoirs, but also has a functional role in vertebrate pathogenesis: an attribute that aligns with the Coincidence of Virulence Hypothesis. This project will identify the ecological and evolutionary roles of mycolactone in watershed ecosystems of French Guiana, a French territory northeast of Brazil, where disease is endemic. Previous assessments of global M. ulcerans genetic diversity reveal the Guiana Shield to be a hotspot of molecular evolution, which supports the hypothesis that African and Australian strains represent recent introductions from a putative Neotropical origin. The research will be accomplished through expeditions to collect aquatic communities along three watersheds for quantifying the diversity of mycolactone producing mycobacteria. At the broadest spatiotemporal scale, the team will conduct comparative genomic research on environmental mycobacteria, including a co-phylogenetic analysis involving a candidate fish host reservoir (guppies), which is now globally distributed due to anthropogenic dispersal. Several integrated mathematical modeling approaches will be used to synthesize project results to determine how molecular evolution of a pathogen toxin leads to human disease through complex ecological interactions across scales. The results will contribute insights into the mechanisms behind establishment, persistence and spread of disease causing agents in naïve host and environmental communities.