title: Correlation of quinolone resistance levels and differences in basal and quinolone-induced expression from three qnrA-containing plasmids.
abstract: This study investigated the effect of copy number and transcriptional level of the qnrA gene on plasmid-mediated quinolone resistance, and the effect of quinolones on qnrA expression, in three clinical isolates of Klebsiella pneumoniae and the corresponding Escherichia coli transconjugants. The copy number of plasmids containing qnrA was analysed and transcriptional studies were performed on transconjugants grown in the presence or absence of ciprofloxacin or moxifloxacin. None of the three clinical isolates was porin-deficient. One isolate contained a mutation in the quinolone resistance-determining region of the gyrA gene (Ser83Phe), but no gyrA mutations were present in the other two isolates, and no mutations were found in parC. Differences in qnrA copy number were observed in K. pneumoniae, but not in the corresponding E. coli transconjugants, although the qnrA gene was located in plasmids with similar mobility and Southern blot RFLP pattern. Differences in qnrA transcription, both at the basal level and following induction by quinolones, were observed among transconjugants. Expression of the qnrA gene correlated well with the level of quinolone (ciprofloxacin and moxifloxacin) resistance in E. coli transconjugants. These data suggest that the main factor determining the resistance level in the transconjugants analysed was the different levels of qnrA expression.
authors.affiliation: Department of Microbiology, School of Medicine, University of Seville, C/Sanchez Pizjuan s/n, 41009 Seville, Spain. jmrodriguez@us.es
authors.forename: J M
authors.initials: JM
authors.lastname: Rodríguez-Martínez
authors.forename: C
authors.initials: C
authors.lastname: Velasco
authors.forename: A
authors.initials: A
authors.lastname: Pascual
authors.forename: I
authors.initials: I
authors.lastname: García
authors.forename: L
authors.initials: L
authors.lastname: Martínez-Martínez
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D001372:Aza Compounds / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics; D015152:Blotting, Northern; D015139:Blotting, Southern; D002939:Ciprofloxacin / Q000494:pharmacology*; D003227:Conjugation, Genetic; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D024841:Fluoroquinolones; D018628:Gene Dosage; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007710:Klebsiella Infections / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D000077266:Moxifloxacin; D010957:Plasmids / Q000235:genetics; D011804:Quinolines / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; D001372:Aza Compounds; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D024841:Fluoroquinolones; C485385:Qnr protein, Klebsiella pneumoniae; D011804:Quinolines; D002939:Ciprofloxacin; D000077266:Moxifloxacin