Genetic mutations in the quinolone resistance-determining region are related to changes in the epidemiological profile of methicillin-resistant Staphylococcus aureus isolates

Abstract

Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) is an important causative agent of nosocomial infections. Mutations in the quinolone resistance-determining regions (QRDRs) of the gyr and par genes have been described. This study aimed to characterise phenotypic and genotypic fluoroquinolone resistance in 69 MRSA isolates of different clonal lineages from hospitals in Rio de Janeiro, Brazil.

Methods: QRDR mutations in the gyrA, gyrB, parC and parE genes were detected by DNA sequencing. Minimum inhibitory concentrations (MICs) for ciprofloxacin and moxifloxacin were determined by broth microdilution. The occurrence of associations between mutations and MICs among the different clonal lineages of MRSA isolates was then verified.

Results: Most isolates from the USA400/ST1/SCCmec IV lineage, but mainly USA100/ST5/SCCmec II isolates, which have been more recently found in Rio de Janeiro hospitals, showed different patterns of mutations, including double mutation in the QRDR of parC (Ser-80⿿⿿⿿Tyr and Glu-84⿿⿿⿿Lys/Gly) and/or gyrA (Ser-84⿿⿿⿿Leu and/or Glu-88⿿⿿⿿Lys) associated with higher moxifloxacin and ciprofloxacin MICs (MIC₉₀, ⿥8⿿mg/L and 256⿿mg/L, respectively). On the other hand, all USA800/ST5/SCCmec IV and the BEC/ST239/SCCmec III isolates, which have disappeared from hospitals, showed single mutations in parC (Ser-80⿿⿿⿿Phe) and gyrA (Ser-84⿿⿿⿿Leu or Glu-88⿿⿿⿿Gly) and lower fluoroquinolones MICs (MIC₉₀, ⿥2⿿mg/L and ⿥16⿿mg/L).

Conclusion: This study highlights an increase in the number and types of mutations in the QRDRs ofgyrA and parC associated with high fluoroquinolones MICs that may be related to changes in the epidemiological profile of MRSA isolates from hospitals in Rio de Janeiro.

Keywords: Clonal lineage; Fluoroquinolones; MRSA; QRDR mutations; gyrA; parC.