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In vitro selection and characterization of Bacillus anthracis mutants with high-level resistance to ciprofloxacin.

by: LB Price, A Vogler, T Pearson, JD Busch, JM Schupp, P Keim
Antimicrob Agents Chemother, Vol. 47, No. 7. (July 2003), pp. 2362-2365.


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Mutants of attenuated Bacillus anthracis with high-level ciprofloxacin resistance were isolated using a three-step in vitro selection. Ciprofloxacin MICs were 0.5 micro g/ml for first-step mutants, which had one of two gyrA quinolone resistance-determining region (QRDR) mutations. Ciprofloxacin MICs were 8 and 16 microg/ml for second-step mutants, which had one of three parC QRDR mutations. Ciprofloxacin MICs for third-step mutants were 32 and 64 microg/ml. Mutants for which MICs were 64 microg/ml had one of two additional mutations within the gyrA QRDR or one of two mutations within the gyrB QRDR. Mutants for which MICs were 32 microg/ml had no additional target modifications but showed evidence of enhanced ciprofloxacin efflux.


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