Relationship between mutations in the coding and promoter regions of the norA genes in 42 unrelated clinical isolates of Staphylococcus aureus and the MICs of norfloxacin for these strains

Schmitz, F.-J.; Hertel, B; Hofmann, B.; Scheuring, Sibylle; Verhoef, J.; Fluit, Ad C.; Heinz, Hans‐Peter; Köhrer, Karl; Jones, Mark

doi:10.1093/jac/42.4.561

Cited by 29 publications

(19 citation statements)

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“…The site of the norA mutation in mutant TP178 that was obtained in vitro was similar to that in clinical isolates. 16) Our observations therefore strongly suggest that such clinically-isolated norA mutants may have appeared in response to selective pressure from environmental chemical agents, such as antiseptics and disinfectants, rather than selective pressure from FQs. The present study has revealed the sites of norA mutations and has also suggested the possible existence of at least one other multidrug-resistance gene in S. aureus.…”

Section: Northern Blotting and Primer Extension Analysismentioning

confidence: 59%

Frequency and Genetic Characterization of Multidrug-Resistant Mutants of Staphylococcus aureus after Selection with Individual Antiseptics and Fluoroquinolones.

Noguchi

Tamura

Narui

et al. 2002

Biological & Pharmaceutical Bulletin

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Section: Northern Blotting and Primer Extension Analysismentioning

confidence: 59%

Frequency and Genetic Characterization of Multidrug-Resistant Mutants of Staphylococcus aureus after Selection with Individual Antiseptics and Fluoroquinolones.

Noguchi

Tamura

Narui

et al. 2002

Biological & Pharmaceutical Bulletin

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“…All mutants selected in vitro showed mutations in the norA promoter region (Table 3 and Fig. 2), many of which were described in the past (9,11,33). The T126A mutation, mapping within the Ϫ35 site of the predicted norA promoter region, was the most frequent mutation found (present in 13/24 mutant strains).…”

Section: Susceptibility Of Clinical Isolates To Biocides Mic and Mbcmentioning

confidence: 85%

Evaluation of Reduced Susceptibility to Quaternary Ammonium Compounds and Bisbiguanides in Clinical Isolates and Laboratory-Generated Mutants of Staphylococcus aureus

Furi

Ciusa

Knight

et al. 2013

Antimicrob Agents Chemother

100

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The MICs and minimum bactericidal concentrations (MBCs) for the biocides benzalkonium chloride and chlorhexidine were determined against 1,602 clinical isolates of Staphylococcus aureus. Both compounds showed unimodal MIC and MBC distributions (2 and 4 or 8 mg/liter, respectively) with no apparent subpopulation with reduced susceptibility. To investigate further, all isolates were screened for qac genes, and 39 of these also had the promoter region of the NorA multidrug-resistant (MDR) efflux pump sequenced. The presence of qacA, qacB, qacC, and qacG genes increased the mode MIC, but not MBC, to benzalkonium chloride, while only qacA and qacB increased the chlorhexidine mode MIC. Isolates with a wild-type norA promoter or mutations in the norA promoter had similar biocide MIC distributions; notably, not all clinical isolates with norA mutations were resistant to fluoroquinolones. In vitro efflux mutants could be readily selected with ethidium bromide and acriflavine. Multiple passages were necessary to select mutants with biocides, but these mutants showed phenotypes comparable to those of mutants selected by dyes. All mutants showed changes in the promoter region of norA, but these were distinct from this region of the clinical isolates. Still, none of the in vitro mutants displayed fitness defects in a killing assay in Galleria mellonella larvae. In conclusion, our data provide an in-depth comparative overview on efflux in S. aureus mutants and clinical isolates, showing also that plasmid-encoded efflux pumps did not affect bactericidal activity of biocides. In addition, current in vitro tests appear not to be suitable for predicting levels of resistance that are clinically relevant.

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“…A point mutation in the norA gene, and also norA overexpression caused by mutations in the promoter region, can increase the MICs of fl uoroquinolones [8,9,14] . Recently, it was also shown that overexpression of the NorA effl ux pump has minimal effect on the MIC of gatifl oxacin [16] .…”

Section: -Methoxyfl Uoroquinolone Resistance In Methicillin-resistanmentioning

confidence: 99%

Molecular Characterization of 8-Methoxyfluoroquinolone Resistance in a Clinical Isolate of Methicillin-Resistant <i>Staphylococcus aureus</i>

Horii¹,

Suzuki

Takeshita³

et al. 2007

Chemotherapy

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Background: Activity of gatifloxacin against clinical isolates of fluoroquinolone-resistant Staphylococcus aureus is more potent than that of other fluoroquinolones such as norfloxacin and levofloxacin. To date, few reports have described high-level resistance to gatifloxacin in clinical isolates of S. aureus, although in vitro studies have shown that mutations in both DNA gyrase and topoisomerase IV were required for gatifloxacin resistance in S. aureus.Methods: Minimum inhibitory concentrations were determined for fluoroquinolones and other antimicrobials in a methicillin-resistant S. aureus isolate that was cultured from blood of a patient with septicemia. Fluoroquinolone resistance was characterized by DNA sequencing and microbiologic assay. Results: The isolate showed high-level resistance to fluoroquinolones including an 8-methoxyfluoroquinolone, gatifloxacin (minimum inhibitory concentration 64 µg/ml). Amino acid mutations of Ser80Tyr and Glu84Lys in GrlA and Ser84Leu and Ser85Pro in GyrA were possibly related to this resistance in methicillin-resistant S. aureus HU2000-062, although efflux may play a minor role in resistance as well. Conclusion: GyrA and GrlA mutations mainly conferred to 8-methoxyfluoroquinolone resistance in this isolate.

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Relationship between mutations in the coding and promoter regions of the norA genes in 42 unrelated clinical isolates of Staphylococcus aureus and the MICs of norfloxacin for these strains

Cited by 29 publications

References 0 publications

Frequency and Genetic Characterization of Multidrug-Resistant Mutants of Staphylococcus aureus after Selection with Individual Antiseptics and Fluoroquinolones.

Frequency and Genetic Characterization of Multidrug-Resistant Mutants of Staphylococcus aureus after Selection with Individual Antiseptics and Fluoroquinolones.

Evaluation of Reduced Susceptibility to Quaternary Ammonium Compounds and Bisbiguanides in Clinical Isolates and Laboratory-Generated Mutants of Staphylococcus aureus

Molecular Characterization of 8-Methoxyfluoroquinolone Resistance in a Clinical Isolate of Methicillin-Resistant <i>Staphylococcus aureus</i>

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