Reversion to susceptibility in a linezolid-resistant clinical isolate of Staphylococcus aureus

Authors:
  • HGHoward S. Gold
    Howard S. Gold
  • ACAmy Cooke
    Amy Cooke
  • LVLata Venkataraman
    Lata Venkataraman
  • GEGeorge M. Eliopoulos
    George M. Eliopoulos
  • RMRobert C. Moellering
    Robert C. Moellering
  • SJStephen G. Jenkins
    Stephen G. Jenkins
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Abstract
Objectives: Linezolid resistance in rare isolates of Staphylococcus aureus has been associated with G2576T mutations in domain V of the 23S rRNA gene. We report the analysis of a clinical S. aureus isolate that developed linezolid resistance (MIC of linezolid of 12 mg/L) after a 25 day course of the drug. Sequencing identified G2576T mutations in four of the five copies of the 23S rRNA gene. Methods: To examine the stability of this resistance, we serially passaged this original isolate 60 times over a 75 day period on antimicrobial-free medium. Results: After 30 passages, the MIC of linezolid had decreased to 8 mg/L and only two of the five copies of the 23S rRNA gene contained the G2576T mutation. After 60 passages, the MIC of linezolid fell to 2 mg/L and only one of the five 23S rRNA gene copies contained the mutation. The original and two passaged staphylococci were indistinguishable by pulsed-field gel electrophoresis. Conclusions: In the absence of antibiotic pressure, linezolid resistance was unstable in a clinical isolate that did not have all copies of the 23S rRNA gene mutated, although a single copy of mutant rDNA was maintained. Gene conversion was probably the mechanism for this reversion, using the wild-type 23S rRNA gene sequences to replace the G2576T mutation by homologous recombination.

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