Article

Selection and characterization of fluoroquinolone-resistant mutants of Campylobacter jejuni using enrofloxacin.

UR86 de Pathologie Aviaire et Parasitologie, Institut National de la Recherche Agronomique, 37380 Nouzilly, France.
Microbial Drug Resistance (impact factor: 2.15). 01/2002; 8(4):335-43. DOI:10.1089/10766290260469606
Source: PubMed

ABSTRACT Significant levels of fluoroquinolone resistance were obtained in Campylobacterjejuni isolates after an unique step of selection using enrofloxacin. An Asp90-to-Asn and a Thr86-to-Ile change in the gyrase subunit GyrA were found associated with a low (MIC < or = 8 /microg/ml) or a high (MIC > or = 16 microg/ml) level of resistance to ciprofloxacin, respectively. An association of both mutations conferred a higher level of resistance (MIC > or = 128 microg/ml). Further steps of selection increased the MICs of fluoroquinolones but did not result in a multiple antibiotic resistance phenotype. The Thr86-to-Ile change was found to confer different levels of resistance, pointing out other mechanisms of resistance. However, sequencing revealed no mutation in gyrB, and several attempts did not enable any amplification of the parC gene coding for topoisomerase IV, suggesting an absence of this secondary target in C. jejuni. In addition, no difference in the major outer membrane protein expression was found among the isolates. Furthermore, the use of the recently identified efflux pump inhibitor Phe-Arg-beta-naphthylamide did not result in a significant decrease of fluoroquinolone MICs or change in the frequency of isolation of enrofloxacin-resistant mutants, and thus appears ineffective against fluoroquinolone-resistant C. jejuni isolates. Results obtained during ciprofloxacin accumulation studies confirmed that efflux probably plays a minor role in fluoroquinolone resistance of C. jejuni.

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Keywords

amplification
 
C. jejuni
 
ciprofloxacin accumulation studies
 
different levels
 
enrofloxacin-resistant mutants
 
fluoroquinolone MICs
 
fluoroquinolone resistance
 
fluoroquinolone-resistant C. jejuni
 
fluoroquinolones
 
identified efflux pump inhibitor Phe-Arg-beta-naphthylamide
 
major outer membrane protein expression
 
MIC
 
MICs
 
multiple antibiotic resistance phenotype
 
parC gene coding
 
significant decrease
 
Significant levels
 
Thr86-to-Ile change
 
topoisomerase IV
 
unique step
 

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