Abstract
The effects on MIC values and the selection of different base substitutions in the quinolone resistance determining region (QRDR) of gyrA were studied on initially ciprofloxacin-susceptible Campylobacter jejuni strains by challenging them to 0.125 mg/L of ciprofloxacin. This ciprofloxacin challenge selected variants with ciprofloxacin MIC levels up to 32 mg/L. Repeated experiments under identical conditions resulted in different responses in MIC levels and alterations in the QRDR of gyrA. A characteristic outcome to ciprofloxacin challenges was the appearance of double peaks in the sequencing chromatograms of QRDR. This finding suggested the coexistence of subpopulations possessing Thr86 --> Ile and/or Asp90 --> Asn mutations alongside the unmutated parent population. In some cases, bacterial variants expressing ciprofloxacin-resistant phenotypes possessed no mutations in their QRDR. These variants were prone to regain susceptibility to ciprofloxacin rapidly after the removal of the selection pressure, whereas the QRDR-mutated variants persisted over several subcultivations in a medium without ciprofloxacin. In conclusion, a low ciprofloxacin concentration of 0.125 mg/L selects a variety of QRDR mutations and also a QRDR-independent resistance mechanism, which may coexist with each other in a C. jejuni population. Persistent ciprofloxacin challenge selects Thr86 --> Ile and/or Asp90 --> Asn mutants.
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