title: Molecular diversity of quinolone resistance in genetically related clinical isolates of Staphylococcus aureus and susceptibility to newer quinolones.
abstract: The genes encoding topoisomerases (gyrA and grlA) and the norA promoter of 100 fluoroquinolone-susceptible and -resistant Staphylococcus aureus clinical isolates obtained in two geographically distant hospitals were analysed. The relationship between mutations found and the susceptibility to newer quinolones was determined. Thirty-nine strains were grouped in seven clones by pulsed-field gel electrophoresis (PFGE). The remaining 61 strains were classified as unrelated strains. In three clones, all strains showed the same grlA-gyrA-norA mutation profiles. Strains in the rest of the groups showed different mutation profiles, even though PFGE indicated that they possessed genetically similar populations. One cluster showed a high level of diversity; five different mutation profiles were detected in the six isolates belonging to this pattern. Two isolates had a Glu84 to Lys mutation in grlA and another isolate had this mutation combined with a Ser84 to Leu mutation in gyrA. Combination of a Ser80 to Phe mutation in grlA and a Ser84 to Leu in gyrA was found in the two other isolates. One of these also had a thymine to a guanine transversion at a position 89 nucleotides upstream of the norA start codon in the norA promoter. These results show that fluoroquinolone resistance in clinical S. aureus strains does not necessarily result from the spread of resistant clones. Fluoroquinolone resistance may develop independently in strains belonging to the same PFGE pattern by accumulation of different mutations over a quinolone-susceptible ancestor wild type or single grlA mutant.
authors.affiliation: Departamento de Genética y Microbiología, Facultad de Medicina, Hospital General Universitario, Universidad de Murcia, Murcia, Spain.
authors.forename: G Y
authors.initials: GY
authors.lastname: Guirao
authors.forename: M C
authors.initials: MC
authors.lastname: Martínez Toldos
authors.forename: B
authors.initials: B
authors.lastname: Mora Peris
authors.forename: M A
authors.initials: MA
authors.lastname: Alonso Manzanares
authors.forename: M N
authors.initials: MN
authors.lastname: Gutiérrez Zufiaurre
authors.forename: J A
authors.initials: JA
authors.lastname: Martínez Andrés
authors.forename: J L
authors.initials: JL
authors.lastname: Muñoz Bellido
authors.forename: J A
authors.initials: JA
authors.lastname: García-Rodríguez
authors.forename: M
authors.initials: M
authors.lastname: Segovia Hernández
mesh_terms: D042462:4-Quinolones; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D015152:Blotting, Northern; D004269:DNA, Bacterial / Q000032:analysis; D016521:Electrophoresis, Gel, Pulsed-Field; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008826:Microbial Sensitivity Tests; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009154:Mutation / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics*
chemical_list: D042462:4-Quinolones; D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C075040:NorA protein, Staphylococcus