Abstract
Background: This study was performed to determine the extended spectrum of quinolone resistance caused by increased mutations within the target enzymes of quinolones. Methods: The minimum inhibitory concentrations (MICs) for ciprofloxacin, sparfloxacin, trovafloxacin and DW286 were determined against 98 ciprofloxacin-resistant Staphylococcus aureus strains. Also, PCR-amplified grlA, grlB, gyrA and gyrB DNA fragments were sequenced and amino acid changes were analyzed. Results: The MIC<sub>50</sub> values of quinolones decreased with later-generation compounds, i.e. ≧64 µg/ml for ciprofloxacin, 16 µg/ml for sparfloxacin, 2 µg/ml for trovafloxacin and 0.25 µg/ml for DW286. Combinations of amino acid changes within GrlA (Ser-80, Tyr-83 or Glu-84), GrlB (Pro-451, Pro-585 or Asp-432) and GyrA (Ser-84, Ser-85 or Glu-88) were constructed. The combination of Ser-80→Phe within GrlA and Ser-84→Leu within GyrA was the fundamental combination in alterations involved in ciprofloxacin resistance, and additional alterations extended quinolone resistance. Conclusion: A larger number of alterations within GrlA and GyrA further extended the spectrum of quinolone resistance.
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