Mutation rate and evolution of fluoroquinolone resistance in Escherichia coli isolates from patients with urinary tract infections

Escherichia coli strains from patients with uncomplicated urinary tract infections were examined by DNA sequencing for fluoroquinolone resistance-associated mutations in six genes: gyrA, gyrB, parC, parE, marOR, and acrR. The 54 strains analyzed had a susceptibility range distributed across 15 dilutions of the fluoroquinolone MICs. There was a correlation between the fluoroquinolone MIC and the number of resistance mutations that a strain carried, with resistant strains having mutations in two to five of these genes. Most resistant strains carried two mutations in gyrA and one mutation in parC. In addition, many resistant strains had mutations in parE, marOR, and/or acrR. No (resistance) mutation was found in gyrB. Thus, the evolution of fluoroquinolone resistance involves the accumulation of multiple mutations in several genes. The spontaneous mutation rate in these clinical strains varied by 2 orders of magnitude. A high mutation rate correlated strongly with a clinical resistance phenotype. This correlation suggests that an increased general mutation rate may play a significant role in the development of high-level resistance to fluoroquinolones by increasing the rate of accumulation of rare new mutations.

Medienart:

Artikel

Erscheinungsjahr:

2003

Erschienen:

2003

Enthalten in:

Zur Gesamtaufnahme - volume:47

Enthalten in:

Antimicrobial agents and chemotherapy - 47(2003), 10 vom: 30. Okt., Seite 3222-32

Sprache:

Englisch

Beteiligte Personen:

Komp Lindgren, Patricia [VerfasserIn]
Karlsson, Asa [VerfasserIn]
Hughes, Diarmaid [VerfasserIn]

Themen:

5E8K9I0O4U
Anti-Bacterial Agents
Anti-Infective Agents
Ciprofloxacin
DNA, Bacterial
DNA Topoisomerases, Type II
EC 5.99.1.3
Fluoroquinolones
Journal Article
Membrane Transport Proteins
N0F8P22L1P
Norfloxacin
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 08.03.2004

Date Revised 13.04.2024

published: Print

Citation Status MEDLINE

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM142479101