Affiliation:
1. Department of Bacterial Pathogenesis and Infection Control, National Institute of Infectious Diseases, Tokyo, Japan
Abstract
ABSTRACT
Plasmid-mediated Qnr and AAC(6′)-Ib-cr have been recognized as new molecular mechanisms affecting fluoroquinolone (FQ) resistance. C316, an
Escherichia coli
strain demonstrating resistance to various FQs, was isolated in Japan. Resistance to FQs was augmented in an
E. coli
CSH2 transconjugant, but PCR failed to detect
qnr
genes, suggesting the presence of novel plasmid-mediated FQ resistance mechanisms. Susceptibility tests, DNA manipulation, and analyses of the gene and its product were performed to characterize the genetic determinant. A novel FQ-resistant gene,
qepA
, was identified in a plasmid, pHPA, of
E. coli
C316, and both
qepA
and
rmtB
genes were mediated by a probable transposable element flanked by two copies of IS
26
. Levels of resistance to norfloxacin, ciprofloxacin, and enrofloxacin were significantly elevated in
E. coli
transformants harboring
qepA
under AcrB-TolC-deficient conditions. QepA showed considerable similarities to transporters belonging to the 14-transmembrane-segment family of environmental actinomycetes. The effect of carbonyl cyanide
m
-chlorophenylhydrazone (CCCP) on accumulation of norfloxacin was assayed in a
qepA
-harboring
E. coli
transformant. The intracellular accumulation of norfloxacin was decreased in a
qepA
-expressing
E. coli
transformant, but this phenomenon was canceled by CCCP. The augmented FQ resistance level acquired by the probable intergeneric transfer of a gene encoding a major facilitator superfamily-type efflux pump from some environmental microbes to
E. coli
was first identified. Surveillance of the
qepA
-harboring clinical isolates should be encouraged to minimize further dissemination of the kind of plasmid-dependent FQ resistance determinants among pathogenic microbes.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
381 articles.
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