title: In vitro selection and characterization of Bacillus anthracis mutants with high-level resistance to ciprofloxacin.
abstract: 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.
authors.affiliation: Department of Biological Sciences, Northern Arizona University, Flagstaff, Arizona 86011-5640, USA.
authors.forename: Lance B
authors.initials: LB
authors.lastname: Price
authors.forename: Amy
authors.initials: A
authors.lastname: Vogler
authors.forename: Talima
authors.initials: T
authors.lastname: Pearson
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Busch
authors.forename: James M
authors.initials: JM
authors.lastname: Schupp
authors.forename: Paul
authors.initials: P
authors.lastname: Keim
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D001408:Bacillus anthracis / Q000187:drug effects* / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002939:Ciprofloxacin / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D005820:Genetic Testing; D066298:In Vitro Techniques; D026901:Membrane Transport Proteins; D008826:Microbial Sensitivity Tests; D020125:Mutation, Missense
chemical_list: D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; C075041:Bmr protein, Bacillus subtilis; D002939:Ciprofloxacin