Abstract

The fim operon is present in most uropathogenic Escherichia coli (UPEC) and is under control of an invertible promoter (fimS) that results in phase switching between ON and OFF orientations. The fim operon encodes type 1 pili (T1P), a critical virulence factor in establishing UTIs, and is known to influence regulation of other virulence factors, yet the underlying genetic mechanisms behind this remain largely unknown. In this thesis, I have characterized the genome-wide protein occupancy and transcriptome of the model UPEC strain, UTI89, in tandem with phenotypic and genotypic analysis of diverse UPEC strains. Additionally, I have investigated the effect of mannosides, which inhibit T1P expression, in passively repressing the fimS ON orientation through an unknown mechanism. This dissertation has further elucidated genetic regulatory networks of pathogenesis by both the phase variable T1P promoter, fimS, and small molecule inhibitors of T1P (mannosides), in UPEC.

Committee Chair

Scott Hultgren

Committee Members

Andrew Kau; Christina Stallings; David Hunstad; Lydia Freddolino; Michael Caparon

Degree

Doctor of Philosophy (PhD)

Author's Department

Biology & Biomedical Sciences (Molecular Microbiology & Microbial Pathogenesis)

Author's School

Graduate School of Arts and Sciences

Document Type

Dissertation

Date of Award

3-13-2026

Language

English (en)

Author's ORCID

https://orcid.org/0000-0001-8724-3213

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Available for download on Saturday, March 11, 2028

Included in

Microbiology Commons

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