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

J Antimicrob Chemother. 2004 Oct;54(4):818-20. doi: 10.1093/jac/dkh423. Epub 2004 Sep 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / pharmacology*
  • Anti-Bacterial Agents / pharmacology*
  • Drug Resistance, Bacterial / genetics*
  • Genes, Bacterial / genetics
  • Linezolid
  • Microbial Sensitivity Tests
  • Mutation
  • Oxazolidinones / pharmacology*
  • RNA, Ribosomal, 23S / genetics*
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / genetics

Substances

  • Acetamides
  • Anti-Bacterial Agents
  • Oxazolidinones
  • RNA, Ribosomal, 23S
  • Linezolid