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Title page for ETD etd-03152019-150554

Type of Document Dissertation
Author Eberly, Allison Rae
URN etd-03152019-150554
Degree PhD
Department Microbiology and Immunology
Advisory Committee
Advisor Name Title
James E. Cassat, MD PhD Committee Chair
David M. Aronoff, MD Committee Member
Douglass B. Clayton, MD Committee Member
Maria Hadjifrangiskou Committee Member
Timothy L. Cover, MD Committee Member
  • metabolomics
  • UPEC
  • UTI
  • biofilm
Date of Defense 2019-03-04
Availability unrestricted
Urinary tract infections (UTIs) are very common, the disease severity can encompass a broad range of clinical diagnoses, including acute cystitis, pyelonephritis, catheter-associated infection, and asymptomatic bacteriuria. UPEC is a Gram-negative facultative anaerobe that forms multi-cellular communities known as biofilms on the surface of catheter material, urinary tract tissues, and within bladder epithelial cells. The formation of biofilms greatly impedes treatment efforts by protecting resident bacteria from external stressors, such as the innate immune response and antibiotic treatment. Biofilm formation by UPEC was studied under different oxygen concentrations and resulted in reduction in oxygen concentration from atmospheric to anoxic conditions coincided with gradual reduction in biofilm formation, and the addition of alternative terminal electron acceptors typically used by E. coli was not sufficient in restoring biofilm formation. Furthermore, there is no pathogenetic signature that predicts if a UPEC strain is asymptomatic or symptom-causing. Furthermore, no studies have examined whether there is a correlation between the biofilm-forming properties of uropathogenic and asymptomatic E. coli isolates. A retrospective study was performed in collaboration with the Vanderbilt Clinical Microbiology Laboratory in which over 300 isolates were collected from monoculture, E. coli-positive urine specimens with corresponding de-identified patient data. The isolates were blindly tested for in vitro extracellular biofilm formation during growth in laboratory media. These assays demonstrated similar variability in the biofilm forming abilities, indicating that there is no specific correlation between biofilm formation and strains that cause symptomatic UTI. However, preliminary metabolomics data of these clinical isolates show metabolic differences between asymptomatic and symptom-causing isolates.

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