Affiliation:
1. Department of Cell and Molecular Biology, Microbiology Programme, Biomedical Center, Uppsala University, S-751 24 Uppsala, Sweden
Abstract
ABSTRACT
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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
283 articles.
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