Reversion to susceptibility in a linezolid-resistant clinical isolate of Staphylococcus aureus.
OBJECTIVE
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.
Meka
Venkata G
VG
Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA. vmeka@bidmc.harvard.edu
Gold
Howard S
HS
Cooke
Amy
A
Venkataraman
Lata
L
Eliopoulos
George M
GM
Moellering
Robert C
RC
Jenkins
Stephen G
SG
D000081:Acetamides / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005798:Genes, Bacterial / Q000235:genetics; D000069349:Linezolid; D008826:Microbial Sensitivity Tests; D009154:Mutation; D023303:Oxazolidinones / Q000494:pharmacology*; D012338:RNA, Ribosomal, 23S / Q000235:genetics*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics
D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D012338:RNA, Ribosomal, 23S; D000069349:Linezolid