title: Proteomic and transcriptomic analysis of linezolid resistance in Streptococcus pneumoniae.
abstract: Linezolid is an oxazolidinone antibiotic that inhibits the initiation of translation. Although resistance to linezolid is an uncommon event, it has been reported in clinical isolates. The genome sequence of Streptococcus pneumoniae linezolid-resistant mutants recently revealed mutations associated with resistance. A proteomic and transcriptomic screen now reveals a possible increase in the metabolism and transport of carbohydrates in these linezolid-resistant S. pneumoniae mutants. Several glycolytic proteins were shown to be overexpressed in the resistant strains, along with other enzymes and transporters involved in the metabolism of sugars. An increase in energy needs appears to be required to sustain extended levels of resistance to linezolid as the disruption of two ABC transporters putatively involved in the import of carbohydrates leads to a 2-fold sensitization to linezolid. Furthermore, the disruption of the catabolite control protein A, a regulator of the metabolism of sugars whose expression is highly increased in one linezolid-resistant mutant, resulted in a 2-fold increase in linezolid susceptibility. This global scale analysis of gene and protein expression profiling highlights metabolism alterations associated with linezolid resistance in S. pneumoniae.
authors.affiliation: Centre de Recherche en Infectiologie and Plate-forme §Protéomique du Centre de génomique de Québec, Université Laval, CHUQ, Pavillon CHUL, 2705 boulevard Laurier, Quebec, QC, Canada, G1V 4G2.
authors.forename: Jie
authors.initials: J
authors.lastname: Feng
authors.forename: Dewan S
authors.initials: DS
authors.lastname: Billal
authors.forename: Andréanne
authors.initials: A
authors.lastname: Lupien
authors.forename: Gina
authors.initials: G
authors.lastname: Racine
authors.forename: Eric
authors.initials: E
authors.lastname: Winstall
authors.forename: Danielle
authors.initials: D
authors.lastname: Légaré
authors.forename: Philippe
authors.initials: P
authors.lastname: Leprohon
authors.forename: Marc
authors.initials: M
authors.lastname: Ouellette
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D015180:Electrophoresis, Gel, Two-Dimensional; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D000069349:Linezolid; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D023303:Oxazolidinones / Q000494:pharmacology*; D020543:Proteome; D040901:Proteomics / Q000379:methods*; D012313:RNA / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000378:metabolism*; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D023303:Oxazolidinones; D020543:Proteome; D012313:RNA; D000069349:Linezolid