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Antimicrobial Agents and Chemotherapy, July 2003, p. 2362-2365, Vol. 47, No. 7
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.7.2362-2365.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

In Vitro Selection and Characterization of Bacillus anthracis Mutants with High-Level Resistance to Ciprofloxacin

Lance B. Price,1,2 Amy Vogler,1 Talima Pearson,1 Joseph D. Busch,1 James M. Schupp,1 and Paul Keim1*

Department of Biological Sciences, Northern Arizona University, Flagstaff, Arizona 86011-5640,1 Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 212052

Received 13 August 2002/ Returned for modification 28 October 2002/ Accepted 26 March 2003

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

* Corresponding author. Mailing address: Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ 86011-5640. Phone: (928) 523-1078. Fax: (928) 523-0639. E-mail: Paul.Keim{at}nau.edu.

Antimicrobial Agents and Chemotherapy, July 2003, p. 2362-2365, Vol. 47, No. 7
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.7.2362-2365.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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