title: Multiple mutations conferring ciprofloxacin resistance in Staphylococcus aureus demonstrate long-term stability in an antibiotic-free environment.
abstract: Two unrelated strains of Staphylococcus aureus, one with a single mutation in grlA, the other with multiple mutations in gyrA, gyrB, grlA, grlB, norA and the norA promoter region, encoding low-level and high-level ciprofloxacin resistance, respectively, were studied. The characterized mutations in these genes were conserved when both strains were passaged for at least 500 generations in an antibiotic-free environment. New, rapidly stabilized mutations and higher MICs were detected for strains passaged in sub-MIC ciprofloxacin concentrations. The seeming irreversibility of quinolone resistance may affect the long-term success of this drug class.
authors.affiliation: Eijkman-Winkler Institute for Clinical Microbiology, University Hospital Utrecht, Utrecht 3584CX, The Netherlands. mjones@thetsn.com
authors.forename: M E
authors.initials: ME
authors.lastname: Jones
authors.forename: N M
authors.initials: NM
authors.lastname: Boenink
authors.forename: J
authors.initials: J
authors.lastname: Verhoef
authors.forename: K
authors.initials: K
authors.lastname: Köhrer
authors.forename: F J
authors.initials: FJ
authors.lastname: Schmitz
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D005838:Genotype; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics*
chemical_list: D000890:Anti-Infective Agents; D002939:Ciprofloxacin