title: Involvement of the CmeABC efflux pump in the macrolide resistance of Campylobacter coli.
abstract: OBJECTIVE
  This study was conducted to examine the role of the CmeABC efflux pump in decreasing the susceptibility of Campylobacter coli to macrolides and ketolides in the context of absence or presence of mutations in the 23S rRNA genes.
  
  
  METHODS
  The cmeB gene was inactivated in strains of C. coli showing two different patterns of erythromycin resistance (low or high level of resistance) associated with the absence or presence of a A2075G mutation in the 23S rRNA genes. MICs of erythromycin, azithromycin, tylosin, telithromycin and ciprofloxacin were compared for wild-type (with or without efflux pump inhibitor) and mutant strains.
  
  
  RESULTS
  The cmeB gene inactivation (or addition of efflux pump inhibitor) led to the restoration of susceptibility of the low-level-resistant strains (no A2075G mutation in the 23S rRNA genes). In the highly resistant strains (A2075G mutation in the 23S rRNA genes), the MICs of erythromycin decreased 128- to 512-fold upon inactivation of the cmeB gene. MICs of azithromycin, tylosin and telithromycin were also affected by both addition of efflux pump inhibitor and cmeB gene inactivation, revealing these molecules as substrates of the CmeABC efflux pump. Compared with azithromycin, MICs of telithromycin drastically decreased upon cmeB gene inactivation even in the presence of a A2075G mutation in 23S rRNA genes.
  
  
  CONCLUSIONS
  The CmeABC efflux pump acts synergically with 23S rRNA mutations to drastically increase the MICs of erythromycin and tylosin in C. coli. In contrast, azithromycin was less affected by efflux and telithromycin, although being a good substrate for the CmeABC efflux pump, was less affected by an A2075G mutation in 23S rRNA genes.
authors.affiliation: Institut National de la Recherche Agronomique, UR086 BioAgresseurs, Santé, Environnement, 37380 Nouzilly, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Cagliero
authors.forename: Christian
authors.initials: C
authors.lastname: Mouline
authors.forename: Sophie
authors.initials: S
authors.lastname: Payot
authors.forename: Axel
authors.initials: A
authors.lastname: Cloeckaert
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017000:Campylobacter coli / Q000187:drug effects*; D024881:Drug Resistance, Bacterial / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D020459:Genes, rRNA; D048628:Ketolides / Q000494:pharmacology; D018942:Macrolides / Q000378:metabolism / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D016254:Mutagenesis, Insertional; D009154:Mutation; D012338:RNA, Ribosomal, 23S / Q000235:genetics
chemical_list: D018528:ATP-Binding Cassette Transporters; D000900:Anti-Bacterial Agents; D048628:Ketolides; D018942:Macrolides; D012338:RNA, Ribosomal, 23S