title: Accumulation of multiple mutations in linezolid-resistant Staphylococcus epidermidis causing bloodstream infections; in silico analysis of L3 amino acid substitutions that might confer high-level linezolid resistance.
abstract: Fifty-six Staphylococcus epidermidis clinical isolates, showing high-level linezolid resistance and causing bacteremia in critically ill patients, were studied. All isolates belonged to ST22 clone and carried the T2504A and C2534T mutations in gene coding for 23SrRNA as well as the C189A, G208A, C209T and G384C missense mutations in L3 protein which resulted in Asp159Tyr, Gly152Asp and Leu94Val substitutions. Other silent mutations were also detected in genes coding for ribosomal proteins L3 and L22. In silico analysis of missense mutations showed that although L3 protein retained the sequence of secondary motifs, the tertiary structure was influenced. The observed alteration in L3 protein folding provides an indication on the putative role of L3-coding gene mutations in high-level linezolid resistance. Furthermore, linezolid pressure in health care settings where linezolid consumption is of high rates might lead to the selection of resistant mutants possessing L3 mutations that might confer high-level linezolid resistance.
authors.affiliation: a Laboratory of Microbiology, School of Medicine , Democritus University of Thrace , Alexandroupolis , Greece.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Ikonomidis
authors.affiliation: a Laboratory of Microbiology, School of Medicine , Democritus University of Thrace , Alexandroupolis , Greece.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Grapsa
authors.affiliation: a Laboratory of Microbiology, School of Medicine , Democritus University of Thrace , Alexandroupolis , Greece.
authors.forename: Charikleia
authors.initials: C
authors.lastname: Pavlioglou
authors.affiliation: a Laboratory of Microbiology, School of Medicine , Democritus University of Thrace , Alexandroupolis , Greece.
authors.forename: Antonia
authors.initials: A
authors.lastname: Demiri
authors.affiliation: a Laboratory of Microbiology, School of Medicine , Democritus University of Thrace , Alexandroupolis , Greece.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Batarli
authors.affiliation: a Laboratory of Microbiology, School of Medicine , Democritus University of Thrace , Alexandroupolis , Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Panopoulou
mesh_terms: D019943:Amino Acid Substitution; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016470:Bacteremia / Q000382:microbiology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics*; D003198:Computer Simulation; D024881:Drug Resistance, Bacterial / Q000235:genetics; D006801:Humans; D000069349:Linezolid / Q000494:pharmacology*; D000090822:Ribosomal Protein L3; D012269:Ribosomal Proteins / Q000737:chemistry / Q000235:genetics*; D013203:Staphylococcal Infections / Q000382:microbiology*; D013212:Staphylococcus epidermidis / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D000090822:Ribosomal Protein L3; D012269:Ribosomal Proteins; D000069349:Linezolid
keywords: Coil; Helix; Multidrug; Polarity; Secondary; Sheet; Size; Tertiary