JAC Advance Access published online on October 2, 2007
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkm345
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Spontaneous mutation frequency and emergence of ciprofloxacin resistance in Campylobacter jejuni and Campylobacter coli
Department of Food and Environmental Hygiene, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
Received 29 March 2007; returned 11 May 2007; revised 16 July 2007; accepted 13 August 2007
* Corresponding author. Tel: +358-9-191-57113; Fax: +358-9-191-57101; E-mail: marja-liisa.hanninen{at}helsinki.fi
Objectives: We analysed the contribution of spontaneous mutation frequency to the evolution of ciprofloxacin resistance and the diversity of mutations in the quinolone resistance-determining region (QRDR) of gyrA and in the intergenic region, cmeR–cmeA, of the CmeABC efflux pump in Campylobacter jejuni and Campylobacter coli.
Methods: The mutation frequency was measured in 11 quinolone-susceptible C. jejuni and 5 C. coli strains, with and without ox bile. MICs and target-specific and efflux-associated mutations were studied for a number of colonies of each strain selected from plates containing 1 mg/L ciprofloxacin.
Results: The spontaneous mutation frequency level among susceptible C. jejuni and C. coli strains ranged from hypomutable (
4 x 10–9) to strongly mutable (7 x 10–3). Ox bile had no effect on mutation frequency. Pre-existing ampicillin and tetracycline resistance increased the MICs of ciprofloxacin for two strains from 0.032–0.125 to 0.5 mg/L. MICs of ciprofloxacin for the colonies selected from plates containing 1 mg/L ciprofloxacin varied from 1 to 16 mg/L, with the Thr-86
Ile or Asp-90Asn mutation detected in the QRDR of gyrA. In 21.5% (14/65) of the selected colonies, no specific mutations existed. Two types of mutations in CmeR promoter-binding inverted sequences were identified both in the parent strains and in the colonies selected from ciprofloxacin plates.
Conclusions: The variation in mutation frequencies between most C. jejuni and C. coli strains was up to 700-fold. Mutation in the QRDR of gyrA or in the intergenic region was not associated with differences in spontaneous mutation frequencies. Previously acquired resistance to tetracycline and ampicillin predisposed strains to high-level ciprofloxacin resistance and to multiple antibiotic resistance.
Key Words: antimicrobials , gyrA , CmeABC
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  M. Hannula and M.-L. Hanninen Effect of putative efflux pump inhibitors and inducers on the antimicrobial susceptibility of Campylobacter jejuni and Campylobacter coli J. Med. Microbiol., July 1, 2008; 57(7): 851 - 855. [Abstract] [Full Text] [PDF]
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