# Urovirulence and fimbrial regulation in Klebsiella quasipneumoniae

> **NIH NIH R21** · UNIVERSITY OF TEXAS DALLAS · 2024 · $197,640

## Abstract

Project Summary
 Urinary tract infection (UTI) and recurrent UTI (rUTI) significantly reduces the quality of life of millions of
women annually and poses a growing health threat due to the increasing prevalence of antibiotic resistant
uropathogenic bacteria. Klebsiella spp. represent the second most common bacterial species isolated from the
urine of women experiencing rUTI but have been largely understudied in the context of rUTI. Within the Klebsiella
genus, Klebsiella pneumoniae is one of the most common human pathogens; however, genome sequence
analysis has revealed that that K. pneumoniae isolates encompass at least three distinct species: K.
pneumoniae, K. variicola and K. quasipneumoniae. Although K. quasipneumoniae strains are commonly isolated
from patients with UTI and encode known virulence factors and antimicrobial resistance genes, no study has
evaluated urovirulence phenotypes of K. quasipneumoniae in an animal model. Indeed, the clinical prevalence
of K. quasipneumoniae in UTI remains unknown.
 Among the virulence factors that Klebsiella spp. possess, type 1 (fim operon) and type 3 (mrk operon)
fimbriae play a crucial role in mediating bacterial adhesion and invasion of host epithelial surfaces. Type 1
fimbriae are widely conserved among Enterobacteriaceae, but the presence of the gene fimK differentiates the
fim operons of Klebsiella spp. from Escherichia coli. In K. pneumoniae, FimK is a regulator of fim operon
expression and is comprised of an N-terminal DNA binding domain that binds the fimS regulatory region and a
conserved C-terminal EAL domain with phosphodiesterase activity. Through sequence alignment of the fim
operons of sequenced K. quasipneumoniae and K. pneumoniae isolates, we have discovered that the fimK gene
of K. quasipneumoniae is truncated and lacks the C-terminal EAL domain. This is important because not only is
fimK a key regulator of fim operon expression, but it is also proposed to co-regulate mrk operon expression by
modulation of cyclic di-GMP levels through its phosphodiesterase activity. We have found that FimK-mediated
regulation of type 1 and type 3 fimbriae is distinct in K. quasipneumoniae due to the absence of the FimK EAL
domain. We hypothesize that because of this regulatory difference, bladder infection dynamics and the
requirement for type 1 versus type 3 fimbriae for bladder colonization may be distinct in K. quasipneumoniae.
 This proposal will address these hypotheses and produce foundational knowledge of K.
quasipneumoniae bladder infection dynamics by i) defining the clinical prevalence of K. quasipneumoniae in UTI
in women, ii) evaluating K. quasipneumoniae rUTI isolates in a mouse model of acute UTI, and iii) evaluating
the role of K. quasipneumoniae type 1 versus type 3 fimbriae and FimK during acute UTI. Taken together, this
work will produce the first foundational knowledge of clinical prevalence and bladder infection dynamics
of the understudied human uropathogen K. quasipneumoniae and...

## Key facts

- **NIH application ID:** 10910160
- **Project number:** 5R21AI169323-02
- **Recipient organization:** UNIVERSITY OF TEXAS DALLAS
- **Principal Investigator:** Nicole Janell De Nisco
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $197,640
- **Award type:** 5
- **Project period:** 2023-08-18 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10910160

## Citation

> US National Institutes of Health, RePORTER application 10910160, Urovirulence and fimbrial regulation in Klebsiella quasipneumoniae (5R21AI169323-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10910160. Licensed CC0.

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