Abstract

The propagation of antibiotic resistance in human pathogens poses a grave threat to global public health. To stem the acquisition of antibiotic resistance genes by pathogens, we must first understand their distribution in non-pathogenic human-associated and environmental microbial communities, identify the antibiotic resistance genes that have most successfully disseminated in the past, and predict which reservoirs and genes have the highest risk of dissemination in the future. Through functional interrogation of the oral and gut metagenomes of uncontacted Amerindians never exposed to pharmacologic-dose antibiotics, we confirmed that antibiotic resistance is an ancient feature of human microbiota, including resistance to semi-synthetic and synthetic antibiotics. Physical linkage with mobile genetic elements suggests that resistance is poised for dissemination upon antibiotic exposure. We also characterized the resistomes of co-localized human gut and environmental microbiota in two resource-poor settings, a rural village of subsistence farmers in El Salvador and a peri-urban slum in Lima, Peru, to identify the genes that have most successfully disseminated between phylogenetically and ecologically disparate microbial habitats, suggest the most likely routes of transfer between humans and the environment, and compare the efficacy of sanitation systems on the removal of AR genes from human waste.

Committee Chair

Gautam Dantas

Committee Members

Justin Fay, Scott Hultgren, Lora Iannotti, Robi Mitra, Jonathan Myers, Audrey Odom

Comments

Permanent URL: https://doi.org/10.7936/K7XS5SPX

Degree

Doctor of Philosophy (PhD)

Author's Department

Biology & Biomedical Sciences (Molecular Genetics & Genomics)

Author's School

Graduate School of Arts and Sciences

Document Type

Dissertation

Date of Award

Winter 12-15-2015

Language

English (en)

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Available for download on Sunday, December 15, 2115

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