title: rplC T460C identified as a dominant mutation in linezolid-resistant Mycobacterium tuberculosis strains.
abstract: The ribosomal L3 protein was identified as a novel target in linezolid (LZD)-resistant Mycobacterium tuberculosis strains. Next-generation sequencing confirmed rplC T460C as the sole mutation in an LZD-resistant M. tuberculosis H37Rv strain selected in vitro. Sequencing analysis revealed the rplC T460C mutation in eight further LZD-resistant isolates (three in vitro-selected mutants and five patient isolates, including isolates from three different patients that developed LZD resistance during treatment) but in none of the susceptible control strains (n = 84).
authors.affiliation: Molecular Mycobacteriology, Research Center Borstel, Borstel, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Beckert
authors.forename: Doris
authors.initials: D
authors.lastname: Hillemann
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Kohl
authors.forename: Jörn
authors.initials: J
authors.lastname: Kalinowski
authors.forename: Elvira
authors.initials: E
authors.lastname: Richter
authors.forename: Stefan
authors.initials: S
authors.lastname: Niemann
authors.forename: Silke
authors.initials: S
authors.lastname: Feuerriegel
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D000069349:Linezolid; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D023303:Oxazolidinones / Q000494:pharmacology*; D000090822:Ribosomal Protein L3; D012269:Ribosomal Proteins / Q000235:genetics*
chemical_list: D000081:Acetamides; D000995:Antitubercular Agents; D004269:DNA, Bacterial; D023303:Oxazolidinones; D000090822:Ribosomal Protein L3; D012269:Ribosomal Proteins; D000069349:Linezolid