title: Linezolid resistance in Staphylococcus aureus: characterization and stability of resistant phenotype.
abstract: Linezolid is an important therapeutic option for treatment of infections caused by glycopeptide- and beta-lactam-resistant gram-positive organisms. Linezolid resistance is caused by mutations within the domain V region of the 23S ribosomal RNA (rRNA) gene, which is present in multiple copies in most bacteria. Among clinical Staphylococcus aureus isolates, there has been only 1 reported case of linezolid resistance. In the present study, this isolate was further characterized by determination of the number of mutant 23S rRNA copies, assessment of the stability of the resistant phenotype, and comparison of its growth characteristics with those of linezolid-susceptible S. aureus. All 5 copies of the 23S rRNA gene contained a G2576U mutation in the domain V region. After serial passage on antibiotic-free medium, the isolate maintained resistance to high concentrations of linezolid. Compared with 2 linezolid-susceptible S. aureus isolates, the linezolid-resistant S. aureus isolate demonstrated no significant differences in in vitro growth characteristics.
authors.affiliation: Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA. spillai@caregroup.harvard.edu
authors.forename: Satish K
authors.initials: SK
authors.lastname: Pillai
authors.forename: George
authors.initials: G
authors.lastname: Sakoulas
authors.forename: Christine
authors.initials: C
authors.lastname: Wennersten
authors.forename: George M
authors.initials: GM
authors.lastname: Eliopoulos
authors.forename: Robert C
authors.initials: RC
authors.lastname: Moellering
authors.forename: Mary Jane
authors.initials: MJ
authors.lastname: Ferraro
authors.forename: Howard S
authors.initials: HS
authors.lastname: Gold
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004275:DNA, Ribosomal / Q000032:analysis; D024881:Drug Resistance, Bacterial / Q000235:genetics; D006801:Humans; D000069349:Linezolid; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D023303:Oxazolidinones / Q000494:pharmacology*; D012338:RNA, Ribosomal, 23S / Q000235:genetics; D017422:Sequence Analysis, DNA; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development*
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D004275:DNA, Ribosomal; D023303:Oxazolidinones; D012338:RNA, Ribosomal, 23S; D000069349:Linezolid