Identification of Urinary Inflammatory Biomarkers for Improved Diagnosis of Urinary Tract Infection in Postmenopausal Women

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dc.contributor.advisorAnderson, Phillip
dc.contributor.advisorDe Nisco, Nicole
dc.contributor.committeeMemberDelk, Nikki
dc.contributor.committeeMemberCampbell, Zachary
dc.contributor.committeeMemberPalmer, Kelli
dc.creatorEbrahimzadeh Pirshahid, Tahmineh
dc.date.accessioned2024-08-30T19:16:36Z
dc.date.available2024-08-30T19:16:36Z
dc.date.created2022-05
dc.date.issued2022-05
dc.date.submittedMay 2022
dc.date.updated2024-08-30T19:16:36Z
dc.description.abstractUrinary tract infection (UTI) is a significant health burden worldwide. UTI has a high rate of recurrence (rUTI), particularly in postmenopausal women. Diagnosis of UTI and rUTI is challenging due to poor specificity and a high false-positive rate of current point-of-care (POC) devices and the 24–72-hour diagnostic window of urine culture – the gold standard of UTI diagnosis. Most UTIs are treated with antibiotic therapy, which is often prescribed before culturebased diagnosis is complete. The overuse of antibiotics in UTI treatment has contributed to the rise in antimicrobial resistance among uropathogenic bacteria that reduces the effectiveness of available antibiotics and complicates UTI and rUTI treatment. To provide more rapid and accurate UTI diagnosis and reduce the overuse of antibiotics, novel POC diagnostic devices with lower false-positive rates than the current state of the art devices must be developed. The pathophysiology of rUTI is a result of an excessive host immune response to uropathogens colonization. While overactive inflammation plays a key role in pathology and severity of UTI, no strategies have been developed to leverage inflammatory cytokines for UTI diagnosis or target inflammation for UTI treatment. The goal of this work was to identify urinary biomarkers for use as potential diagnostic markers and therapeutic targets for UTI and rUTI in postmenopausal women. We investigated the role of different inflammatory markers in rUTI in a controlled cohort of postmenopausal women. We found that urinary levels of inflammatory molecules, PGE2, IL-8, IL-18, IL-1β, and MCP-1 are significantly elevated in the urine of patients with active rUTI compared to the patients with no UTI history. Logistic regression analysis revealed that PGE2, IL8, IL-13 combined model was the best performing model in predicting rUTI status. Furthermore, time-to-relapse analysis indicated that PGE2, but not IL-8 or IL-13, was a strong predictor of UTI recurrence in postmenopausal women. The risk of rUTI relapse was 3.6 times higher in women with above-median urinary PGE2 levels than with below-median levels. Taken together, these data suggest that urinary IL-8, IL-13, and PGE2 may be powerful diagnostic and prognostic biomarkers for the detection of rUTI in postmenopausal women.
dc.format.mimetypeapplication/pdf
dc.identifier.uri
dc.identifier.urihttps://hdl.handle.net/10735.1/10116
dc.language.isoen
dc.subjectBiology, Molecular
dc.subjectBiology, Cell
dc.subjectBiology, Microbiology
dc.titleIdentification of Urinary Inflammatory Biomarkers for Improved Diagnosis of Urinary Tract Infection in Postmenopausal Women
dc.typeThesis
dc.type.materialtext
local.embargo.lift2024-05-01
local.embargo.terms2024-05-01
thesis.degree.collegeSchool of Natural Sciences and Mathematics
thesis.degree.departmentBiology - Molecular and Cell Biology
thesis.degree.grantorThe University of Texas at Dallas
thesis.degree.namePHD

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