Antibiotic Resistance: Development and Dissemination in vitro and in the Marine Environment

Korry, Benjamin Joseph

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Overview

Year:: 2022
Contributor:: Korry, Benjamin Joseph (creator); Belenky, Peter (Advisor); Fairbrother, William (Reader); Plavicki, Jessica (Reader); Weinreich, Daniel (Reader); Gomez-Chiarri, Marta (Reader); Brown University. Biology and Medicine: Pathobiology (sponsor)
Genre:: theses
Subject:: Bacteria; Microbiology; microbiome; Antibiotics; Metagenomics; Metatranscriptomics; shotgun metagenomics; antimicrobial resistance; Microbial ecology (Environmental microbiology)
Extent:: Xii, 203 p.

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Abstract:: Antimicrobial resistance poses a global challenge to human health that is only expected to increase without significant treatment innovations. Novel therapeutic strategies are needed for both treating bacterial infections and preventing the spread and development of resistance. In order to more effectively prevent the emergence of new resistant pathogens, we must understand how resistance develops, where it persists in environmental settings, and how antimicrobial therapy impacts resistance gene expression and selection within the microbiome. In this thesis, we looked at antimicrobial resistance at three different scales; in vitro, in mice, and in the marine environment. First, we utilized traditional microbiology assays combined with high throughput sequencing techniques to describe the process by which genotoxic agents induce a spectrum of stress-specific target-resistance mutations to spectinomycin in Bacillus subtilis. Additionally, we showed that the fitness of individual mutations and their ability to persist in a mixed population is determined by the local antibiotic concentration. The marine environment has been shown to be an important reservoir of antimicrobial resistant bacteria; thus, we studied the dynamics of antimicrobial resistance within the microbiota of marine life in coastal New England waters. We used a shotgun metagenomic sequencing approach to analyze the microbiomes and resistance gene content within the gastrointestinal tract of seven marine species. We found that antibiotic resistance is more prevalent in fish occupying higher trophic levels, and that the presence of resistance genes is positively correlated with the abundance of Proteobacteria within the gut. Finally, we treated mice with three classes of antibiotics to examine how antibiotic therapy impacts the murine resistome. Applying a metatranscriptomic sequencing approach, we showed evidence of targeted resistance gene activity towards β-lactam and tetracycline class antibiotics. Overall, this thesis provides novel insights into the development of resistance through mutagenesis, the role of the marine environment as a reservoir of resistance, and the transcriptional response of the resistome to antibiotic treatment.
Notes:: Thesis (Ph. D.)--Brown University, 2022

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Citation

Korry, Benjamin Joseph, "Antibiotic Resistance: Development and Dissemination in vitro and in the Marine Environment" (2022). Pathobiology Theses and Dissertations. Brown Digital Repository. Brown University Library. https://repository.library.brown.edu/studio/item/bdr:59err4hr/

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Pathobiology Theses and Dissertations

Theses and Dissertations for the Pathobiology department.
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