title: Telithromycin activity is reduced by efflux in Streptococcus pyogenes.
abstract: OBJECTIVE
  To investigate whether telithromycin is a substrate for efflux pumps in Streptococcus pyogenes.
  
  
  METHODS
  The distribution of telithromycin MICs was analysed for two distinct collections of Italian (n=486) and Spanish (n=210) S. pyogenes strains. The effect of an efflux mechanism was investigated using [(3)H]telithromycin.
  
  
  RESULTS
  Telithromycin MIC ranges were < or = 0.004-0.06 mg/L (MIC(50) and MIC(90), 0.01 mg/L) in erythromycin-susceptible strains (lacking both mef and erm genes) and 0.01-1 mg/L (MIC(50) and MIC(90), 0.5 mg/L) in strains endowed with the M phenotype and expressing the mef(A) gene. A distinct telithromycin efflux was detected in the strains expressing the mef(A) gene, but not in those expressing the erm(B) gene, nor in the susceptible strains lacking mef(A) or erm genes. Efflux reversibility by addition of an inhibiting compound (sodium arsenate) was demonstrated. An msr-like sequence was also found in all strains effluxing telithromycin, but not in the others.
  
  
  CONCLUSIONS
  This study shows that telithromycin can be removed from S. pyogenes by efflux. That the efflux is related to the presence of the mef(A) gene is demonstrated, but-owing to the increasingly evident complexity of S. pyogenes efflux systems-the possibility that other genes may contribute to the efflux cannot be excluded.
authors.affiliation: Servicio de Microbiología, Hospital Universitario Ramón y Cajal, Carretera. de Colmenar, Km 9.1, 28034-Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Cantón
authors.forename: Annarita
authors.initials: A
authors.lastname: Mazzariol
authors.forename: María-Isabel
authors.initials: MI
authors.lastname: Morosini
authors.forename: Fernando
authors.initials: F
authors.lastname: Baquero
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cornaglia
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001149:Arsenates; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism; D024881:Drug Resistance, Bacterial / Q000235:genetics* / Q000502:physiology*; D015870:Gene Expression; D048628:Ketolides / Q000378:metabolism / Q000494:pharmacology*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D008826:Microbial Sensitivity Tests; D010641:Phenotype; D013297:Streptococcus pyogenes / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001149:Arsenates; D001426:Bacterial Proteins; D002352:Carrier Proteins; D048628:Ketolides; C117866:MefA protein, Streptococcus; D008565:Membrane Proteins; C009277:sodium arsenate; C106791:telithromycin