Journal Article

Spontaneous mutation frequency and emergence of ciprofloxacin resistance in <i>Campylobacter jejuni</i> and <i>Campylobacter coli</i>

Marja-Liisa Hänninen and Minna Hannula

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 60, issue 6, pages 1251-1257
Published in print December 2007 | ISSN: 0305-7453
Published online October 2007 | e-ISSN: 1460-2091 | DOI: https://dx.doi.org/10.1093/jac/dkm345
Spontaneous mutation frequency and emergence of ciprofloxacin resistance in Campylobacter jejuni and Campylobacter coli

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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 × 10−9) to strongly mutable (∼7 × 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-90→Asn 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.

Keywords: antimicrobials; gyrA; CmeABC

Journal Article.  4167 words. 

Subjects: Medical Oncology ; Critical Care

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