| The increased use of antibiotics in human medicine and agriculture over the past decades has introduced significant selective pressures on bacterial populations in virtually all human-associated environments and lead to the evolution of multidrug-resistant bacteria that compromise our ability to treat infectious disease. Due to the high likelihood of contact and genetic exchange with pathogens during disease progression, the mammalian gut microbiota is considered one of the most accessible reservoirs of resistance determinants. The spread of resistant organisms and their genes occurs not only between humans via direct contact, but can also be disseminated into and from animal populations and environments exposed to human activities, with important consequences for human health and disease. The goal of my dissertation was to understand the mechanisms by which antimicrobial resistance determinants are exchanged between gut-associated communities and the environment, and to determine the role of human activity in these dissemination patterns. To this end, I characterized bacterial communities and resistomes in (1) human, animal, and environmental samples from a shantytown in Lima, Peru---an area representative of many urban developing country settings---and (2) wild baboon populations from Southern Africa that have little or no contact with human populations. Collectively, I show that (1) there is large, shared pool of resistance genes shared between humans at the household and community level; (2) Sewage microbial communities are novel, diverse, and significantly different from the human fecal communities that serve as their input; (3) Antibiotic resistance is an ancient feature of primate gut metagenomes. Future work should be aimed at understanding the biotic and abiotic factors that affect the movement of ARGs from environmental reservoirs into pathogenic strains through real-time monitoring of environmental resistomes and pathogenic strains in the hospital and community settings. |
