Theses and Dissertations

ORCID

https://orcid.org/0000-0003-1533-6095

Advisor

Jordan, Heather

Committee Member

Thornton, Justin

Committee Member

Gout, Jean-Francois

Committee Member

Benbow, Eric

Date of Degree

12-12-2025

Original embargo terms

Immediate Worldwide Access

Document Type

Dissertation - Open Access

Major

Biological Sciences

Degree Name

Doctor of Philosophy (Ph.D.)

College

College of Arts and Sciences

Department

Department of Biological Sciences

Abstract

Mycobacterium ulcerans, the causative agent of Buruli ulcer, produces mycolactone, a polyketide toxin traditionally studied for its role in human pathogenesis. This dissertation presents a comprehensive spatiotemporal analysis of M. ulcerans and mycolactone producing mycobacteria (MPM) ecology in the Americas and also reveals mycolactone's role in the environment as a microbial community regulator. Through comparative studies in French Guiana (endemic) and the southeastern United States (non-endemic), combined with experimental microcosm investigations, this research contributes to environmental pathogen ecology understanding. Environmental surveillance across 2,226 samples from French Guiana revealed complete MPM restriction to freshwater environments, with zero detections from 1,226 coastal samples despite extensive sampling. Temporal analysis demonstrated dramatic seasonal fluctuations, with concentrations varying by 34,000-fold within single ecosystems in the southeastern United States. Spatial distribution patterns consistently showed downstream concentration effects, with lower river reaches yielding 31.5% detection rates compared to zero to 0.6% in upper reaches across all river systems studied. Comparative analysis revealed a regional difference where the southeastern United States harbors genetically diverse MPM populations, identical to those causing endemic disease, without corresponding human transmission. Variable Number Tandem Repeat analysis identified M. ulcerans genotypes A through D and M. liflandii across non-endemic regions, indicating broader global distribution than previously recognized. Microcosm experiments of mycolactone's ecological functions provided evidence that this compound serves as an environmental weapon. Mycolactone treatment caused site-specific differences in microbial community composition, with ten taxa showing significant differential abundance. The selective reduction of Gram-negative bacteria possessing quorum sensing machinery, combined with enrichment of metabolically versatile taxa, demonstrates that mycolactone provides competitive advantages through targeted suppression of bacterial competitors. This research transforms mycolactone from an understood virulence factor into a recognized environmental effector molecule, opening new research directions for understanding pathogen ecology and developing targeted intervention strategies.

Sponsorship (Optional)

NSF-NIH-NIFA Ecology and Evolution of Infectious Disease grant DEB 1911457

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