JAC Advance Access originally published online on September 3, 2004
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Journal of Antimicrobial Chemotherapy 2004 54(4):818-820; doi:10.1093/jac/dkh423
JAC vol.54 no.4 © The British Society for Antimicrobial Chemotherapy 2004; all rights reserved
Reversion to susceptibility in a linezolid-resistant clinical isolate of Staphylococcus aureus
1 Division of Infectious Diseases,, and 3 Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA; 2 Department of Pharmacy, Carolinas Medical Center, Charlotte, NC; 4 Division of Microbiology and Immunology, Department of Pathology, Carolinas Medical Center, Charlotte, NC, USA
* Correspondence address. Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine Bldg, Room 219, 4 Blackfan Circle, Boston, MA 02115, USA. Tel: +1-617-667-0039; Fax: +1-617-975-5235; Email: vmeka{at}bidmc.harvard.edu
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.
Keywords: G2576T mutation , 23S rRNA gene , gene conversion
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