title: Elevated linezolid resistance in clinical cfr-positive Staphylococcus aureus isolates is associated with co-occurring mutations in ribosomal protein L3.
abstract: 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.
authors.affiliation: Trius Therapeutics, Inc., 6310 Nancy Ridge Drive, Suite 105, San Diego, CA 92121, USA.
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Locke
authors.forename: Gracia
authors.initials: G
authors.lastname: Morales
authors.forename: Mark
authors.initials: M
authors.lastname: Hilgers
authors.forename: Kedar
authors.initials: K
authors.lastname: G C
authors.forename: Shahad
authors.initials: S
authors.lastname: Rahawi
authors.forename: Juan
authors.initials: J
authors.lastname: José Picazo
authors.forename: Karen Joy
authors.initials: KJ
authors.lastname: Shaw
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Stein
mesh_terms: 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
chemical_list: D000081:Acetamides; D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D023303:Oxazolidinones; D000090822:Ribosomal Protein L3; D012269:Ribosomal Proteins; D008780:Methyltransferases; D000069349:Linezolid