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

@article{citeulike:3729234, 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. 10.1093/jac/dkh423}, author = {Meka, Venkata G. and Gold, Howard S. and Cooke, Amy and Venkataraman, Lata and Eliopoulos, George M. and Moellering, Robert C. and Jenkins, Stephen G.}, citeulike-article-id = {3729234}, citeulike-linkout-0 = {http://dx.doi.org/10.1093/jac/dkh423}, citeulike-linkout-1 = {http://jac.oxfordjournals.org/content/54/4/818.abstract}, citeulike-linkout-2 = {http://jac.oxfordjournals.org/content/54/4/818.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/15347637}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=15347637}, day = {1}, doi = {10.1093/jac/dkh423}, issn = {0305-7453}, journal = {J. Antimicrob. Chemother.}, keywords = {2}, month = {October}, number = {4}, pages = {818--820}, posted-at = {2009-11-11 15:52:25}, priority = {2}, title = {Reversion to susceptibility in a linezolid-resistant clinical isolate of Staphylococcus aureus}, url = {http://dx.doi.org/10.1093/jac/dkh423}, volume = {54}, year = {2004} }

TY - JOUR ID - citeulike:3729234 L3 - citeulike-article-id:3729234 N2 - 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. 10.1093/jac/dkh423 IS - 4 JF - J. Antimicrob. Chemother. SN - 0305-7453 EP - 820 TI - Reversion to susceptibility in a linezolid-resistant clinical isolate of Staphylococcus aureus VL - 54 SP - 818 KW - 2 AU - Meka, Venkata AU - Gold, Howard AU - Cooke, Amy AU - Venkataraman, Lata AU - Eliopoulos, George AU - Moellering, Robert AU - Jenkins, Stephen PY - 2004/10/01/ UR - http://dx.doi.org/10.1093/jac/dkh423 ER -