Elevated linezolid resistance in clinical cfr-positive Staphylococcus aureus isolates is associated with co-occurring mutations in ribosomal protein L3.
Resistance to linezolid (LZD) occurs through mutations in 23S rRNA and ribosomal proteins L3 and L4 or through methylation of 23S rRNA by Cfr. Here we report novel L3 mutations, ΔSer145/His146Tyr and ΔMet169-Gly174, co-occurring with cfr in LZD-resistant Staphylococcus aureus isolates recovered from a hospital outbreak in Madrid, Spain. LZD MIC values (16, 32, or 64 μg/ml) correlated with the presence and severity of the L3 mutation. All isolates had TR-700 (torezolid) MIC values of ≤ 2 μg/ml.
Locke
Jeffrey B
JB
Trius Therapeutics, Inc., 6310 Nancy Ridge Drive, Suite 105, San Diego, CA 92121, USA.
Morales
Gracia
G
Hilgers
Mark
M
G C
Kedar
K
Rahawi
Shahad
S
José Picazo
Juan
J
Shaw
Karen Joy
KJ
Stein
Jeffrey L
JL
D000081:Acetamides / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D000069349:Linezolid; D008780:Methyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D009154:Mutation; D023303:Oxazolidinones / Q000494:pharmacology*; D000090822:Ribosomal Protein L3; D012269:Ribosomal Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics
D000081:Acetamides; D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D023303:Oxazolidinones; D000090822:Ribosomal Protein L3; D012269:Ribosomal Proteins; D008780:Methyltransferases; D000069349:Linezolid