# Investigating a Novel Co-regulation of Multi-Drug Efflux Pumps and Polysaccharide Capsule in E. coli

> **NIH NIH K08** · LURIE CHILDREN'S HOSPITAL OF CHICAGO · 2020 · $188,478

## Abstract

PROJECT SUMMARY
In this application, I am requesting a career development award to support my research proposal titled
“Investigating a Novel Co-regulation of Multi-Drug Efflux Pumps and Polysaccharide Capsule in E. coli.” I will
be undertaking this work under the mentorship of Dr. Patrick Seed at Duke University. The aims of this
proposal arose out of my interest in identifying virulence specific factors that can be used as targets for new
classes of antimicrobials against Gram negative organisms. Uropathogenic E. coli (UPEC) is one of the most
common Gram negative and a major cause of urinary tract infection (UTI). However, rapidly rising antibiotic
resistance threatens the effectiveness of all commonly used antibiotics. In addition the global rise of the multi-
drug resistant (MDR) UPEC clonal subtype ST131 has been termed an urgent threat to public health by the
Centers for Disease Control. Together this underscores the critical need to identify new antimicrobial
strategies. Since most cases of community acquired UTI occur in patients with an intact immune system an
alternative approach to treating such infections would be to render the bacteria susceptible to natural immune
clearance. We have identified a highly potent small molecule inhibitor of E. coli capsule biogenesis that targets
a transcriptional regulator of an MDR efflux pump. This proposal centers on the hypothesis that this capsule
inhibitor uniquely binds to the efflux pump transcriptional regulator to control E. coli polysaccharide capsule
expression through a novel co-regulatory pathway that results in decreased virulence and increased
susceptibility to the host immune system. This study will test the hypothesis by investigating the binding of
capsule inhibitor to the transcriptional regulator, by identifying the components of the co-regulatory pathway
and by determining the role of the transcriptional regulator in establishment and persistence of UTI. Dr. Seed
will be providing mentorship and expertise in the field of molecular microbial pathogenesis, microbial genomics
and the murine model of UTI. I have worked with Dr. Seed since 2011 as a pediatric infectious disease fellow
and will continue to do so as junior faculty. Duke University is a world-class research institute with numerous
support systems for junior investigators which will be vital for my transition to being an independent
investigator. My long term career goal is to be independently funded leading my own lab focused on using
molecular approaches to identify mechanisms of bacterial pathogenesis and antimicrobial resistance and to
use this knowledge to identify novel targets for pathogen/disease-specific anti-infectives. This award will
enable me to build upon the research foundation I have developed thus far and be exceptionally well poised to
transition to independence.

## Key facts

- **NIH application ID:** 9857473
- **Project number:** 5K08AI123524-04
- **Recipient organization:** LURIE CHILDREN'S HOSPITAL OF CHICAGO
- **Principal Investigator:** Mehreen Arshad
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $188,478
- **Award type:** 5
- **Project period:** 2017-01-18 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9857473

## Citation

> US National Institutes of Health, RePORTER application 9857473, Investigating a Novel Co-regulation of Multi-Drug Efflux Pumps and Polysaccharide Capsule in E. coli (5K08AI123524-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9857473. Licensed CC0.

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