Mutations in ribosomal protein L3 are associated with oxazolidinone resistance in staphylococci of clinical origin.
Following recent reports of ribosomal protein L3 mutations in laboratory-derived linezolid-resistant (LZD(r)) Staphylococcus aureus, we investigated whether similar mutations were present in LZD(r) staphylococci of clinical origin. Sequence analysis of a variety of LZD(r) isolates revealed two L3 mutations, DeltaSer145 (S. aureus NRS127) and Ala157Arg (Staphylococcus epidermidis 1653059), both occurring proximal to the oxazolidinone binding site in the peptidyl transferase center. The oxazolidinone torezolid maintained a >or=8-fold potency advantage over linezolid for both strains.
Locke
Jeffrey B
JB
Trius Therapeutics, Inc., San Diego, CA 92121, USA.
Hilgers
Mark
M
Shaw
Karen Joy
KJ
D000081:Acetamides / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites / Q000235:genetics / Q000502:physiology; D024881:Drug Resistance, Bacterial / Q000235:genetics* / Q000502:physiology; D000069349:Linezolid; D009154:Mutation / Q000235:genetics*; D023303:Oxazolidinones / Q000378:metabolism / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D012338:RNA, Ribosomal, 23S / Q000235:genetics; D000090822:Ribosomal Protein L3; D012269:Ribosomal Proteins / Q000737:chemistry / Q000235:genetics*; D013203:Staphylococcal Infections / Q000382:microbiology*; D013210:Staphylococcus / Q000187:drug effects* / Q000235:genetics*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics; D013777:Tetrazoles / Q000378:metabolism / Q000494:pharmacology
D000081:Acetamides; D023303:Oxazolidinones; D012338:RNA, Ribosomal, 23S; D000090822:Ribosomal Protein L3; D012269:Ribosomal Proteins; D013777:Tetrazoles; C546016:tedizolid; D000069349:Linezolid