Date of Award

2023

Degree Type

Thesis

Degree Name

Master of Science in Biological and Environmental Sciences (MSBES)

Specialization

Cell and Molecular Biology

Department

Cell & Molecular Biology

First Advisor

Jodi L. Camberg

Abstract

Uropathogenic Escherichia coli (UPEC) are the leading cause of urinary tract infections (UTIs). In about a quarter of these cases the patient experiences reoccurring infection after treatment with antibiotics. The prevalence of reoccurrence may be attributed to the ability of some UPEC populations to enter a growth state where they are tolerant to antibiotic treatment. In reduced metabolic, dormant, and quiescent states bacteria are less susceptible to antibiotics that target critical growth pathways, allowing for prolonged survival. In Manuscript I, we investigate antibiotic tolerance in the quiescent UPEC strain CFT073 in vitro. We demonstrate that during quiescence UPEC are tolerant to first line therapies used in the treatment of UTIs, as well as various other broad spectrum treatment options. We also show that introducing a molecule that promotes proliferation, such as succinate or a mixture of amino acids L-Met and L-Lys, in conjunction with antibiotic exposure enhances susceptibility in quiescent UPEC populations. Our findings demonstrate that quiescent UPEC cells are tolerant to various antibiotics in vitro and that susceptibility can be restored in these populations through a combination treatment of an antibiotic and a proliferant cue.

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