# Mechanism of the Fluoroquinolone Resistance Acquisition in Enterobacteria

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2024 · $703,709

## Abstract

ABSTRACT
 Recent pandemic spread of antimicrobial resistance is highly alarming. Fluoroquinolones (FQ) are
broadly used by clinicians for treatment of urinary tract infections, but FQ resistance levels in Escherichia coli
(the main uropathogen) are reaching 15-35%. FQ targets DNA gyrase (GyrAB) and topoisomerase IV
(ParCE), complexes that ensure maintenance of nucleoid super-coiling and structure in states appropriate for
replication and partitioning. The FQ resistance acquisition primarily emerges by structural alteration of the
target proteins with multiple mutations in so-called quinolone-resistance determining regions (QRDR) - two
mutations in GyrA (usually Ser83Leu and Asp87Asn) that are tightly coupled to the presence of at least one
mutation in ParC (usually Ser80Ile). We hypothesize that some clinical E. coli strains are more prone than
others to acquire and, also, to spread or transmit the FQ resistance. Surprisingly, the most common
uropathogenic groups of E. coli appear to demonstrate certain restraints to becoming FQ resistant, probably
due to some physiological barriers for the sequential structural alteration of GyrA and ParC. We discovered
that, instead, that urinary FQ resistant isolates can emerge by acquisition of genes already carrying the full
set of QRDR changes, demonstrating for the first time that high-level FQ resistance can be transmitted
between clinical strains of unrelated clonal groups. This, for example, was the mechanism of recent
emergence of new pandemic FQ resistant clonal group of E. coli – ST1193 that spread globally with last
decade. Here we will study whether there is a clonal association between the ability of clinical E. coli strains
to acquire and spread in nature the full set of QRDR mutations sequentially or, alternatively, by gene transfer
and what could be potential physiological factors that either promote or restrain the FQ resistance
emergence, transmission and spread among uropathogenic E. coli.

## Key facts

- **NIH application ID:** 10806964
- **Project number:** 5R01AI150152-04
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** EVGENI Veniaminovic SOKURENKO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $703,709
- **Award type:** 5
- **Project period:** 2021-04-06 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10806964

## Citation

> US National Institutes of Health, RePORTER application 10806964, Mechanism of the Fluoroquinolone Resistance Acquisition in Enterobacteria (5R01AI150152-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10806964. Licensed CC0.

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