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ORCID

http://orcid.org/0000-0003-2012-4492

Date of Award

Summer 8-15-2021

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Molecular Microbiology & Microbial Pathogenesis)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

Urinary tract infections (UTIs) can be highly recurrent, and the mechanism(s) governing recurrence susceptibility are mostly unknown. Here I demonstrate bladder epithelial (urothelial)-intrinsic trained immunity as part of a differential mucosal remodeling response to an initial UTI. I established urothelial stem cell (USC) lines from isogenic mice with different UTI histories (naïve, chronic, or self-resolving) and discovered 2880 differential genome-accessible regions, indicating differential epigenetic reprogramming dependent on infection history. Differentiation of USC lines in vitro resulted in polarized urothelial cultures that recapitulated distinct remodeling morphologies seen in vivo and exhibited altered gene expression, including genes involved in cell death pathways. Our work may in part explain the clinical observation that a history of prior UTI is a risk factor for recurrent UTI and may lead to novel therapeutic strategies.

Language

English (en)

Chair and Committee

Scott J. Hultgren

Committee Members

Thomas J. Hannan, David Sibley, Christina Stallings, Ting Wang,

Available for download on Friday, August 19, 2022

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