title: Introduction of a norA promoter region mutation into the chromosome of a fluoroquinolone-susceptible strain of Staphylococcus aureus using plasmid integration.
abstract: It has been postulated that a mutation 11 bp 3' to the -10 motif of the norA promoter is involved in the increased expression of the gene observed in some strains of Staphylococcus aureus exhibiting efflux-related fluoroquinolone resistance. Introduction of this mutation into the chromosome of a fluoroquinolone-susceptible strain by plasmid integration resulted in the minimum inhibitory concentrations of NorA substrates being increased, fluoroquinolone uptake being reduced, and norA expression being enhanced. Diffuse hybridization of norA and integrating vector probes at a similar molecular weight range, higher than that of the norA transcript, was observed in the integrant, suggesting the possibility of a plasmid-based promoter contributing to norA expression. The ratio of the quantity of this transcript, which was also observed in the parent strain of the integrant, to the quantity of primary norA transcript was 0.14, demonstrating that it was unlikely that this mRNA species contributed significantly to the results observed. It is more likely that the introduced promoter region mutation does affect the expression of norA.
authors.affiliation: The John D. Dingell Department of Veteran's Affairs Medical Center, Division of Infectious Diseases, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. gkaatz@juno.com
authors.forename: G W
authors.initials: GW
authors.lastname: Kaatz
authors.forename: S M
authors.initials: SM
authors.lastname: Seo
authors.forename: T J
authors.initials: TJ
authors.lastname: Foster
mesh_terms: D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D004352:Drug Resistance, Microbial / Q000235:genetics; D015365:Enoxacin / Q000493:pharmacokinetics / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010957:Plasmids / Q000235:genetics; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D013211:Staphylococcus aureus / Q000145:classification / Q000187:drug effects* / Q000235:genetics
chemical_list: D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D015365:Enoxacin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; C075040:NorA protein, Staphylococcus