Effects of low-level ciprofloxacin challenge in the in vitro development of ciprofloxacin resistance in Campylobacter jejuni

Microbial Drug Resistance : MDR : Mechanisms, Epidemiology, and Disease
Minna Hannula, Marja-Liisa Hänninen

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-indepe...Continue Reading

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Citations

Sep 13, 2013·Microbiology·Heidi HyytiäinenMarja-Liisa Hänninen

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