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The Identification of Sources and Genomic Characteristics of Pandemic Extraintestinal Pathogenic Escherichia coli

Abstract

This dissertation investigates the epidemiologic and microbiologic features of extraintestinal pathogenic Escherichia coli (ExPEC) organisms, with a particular emphasis on antimicrobial drug resistance (AMR) associated with these ExPECs. The first section and the second section (Chapter 2 and Chapter 3) describes the risk factors for healthy adults to carry drug-resistant E. coli in their gut. Chapter 2 presents an overview of what has been described in the literature on risk factors for fecal carriage of drug-resistant E. coli. Chapter 3 focuses on a study we conducted on campus here at the University of California, Berkeley to examine risk factors for carriage of drug-resistant E. coli using a penalized regression model. Chapter 4 describes findings based on molecular epidemiologic and computational biologic methods to investigate genetic features associated with the lack of carriage of drug-resistance genes in a major pandemic lineage of ExPEC, ST95. The focus on a lineage that lacks drug-resistance genes was an attempt to characterize counterfactual genetic factors associated with AMR ExPECs that may help to better understand why the prevalence of AMR infections are caused by a limited set of ExPEC lineages. We were able to determine that certain dietary behavior and travel destinations can contribute to colonization with drug-resistant E. coli. Such knowledge could be potentially used to devise prevention of acquisition of drug-resistant E. coli. We also found potential bacterial mechanisms to resist acquiring drug resistant genes. Such knowledge could be exploited to devise biologic interventions to interrupt E. coli from gaining drug-resistance genes. In conclusion, this dissertation work highlights the importance of global bacterial drug resistant infectious disease problem and opened a path towards further studies that may ultimately lead to the creation of new prevention strategies against AMR infections.

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