Molecular basis of macrolide resistance in Campylobacter: role of efflux pumps and target mutations

J Antimicrob Chemother. 2005 Sep;56(3):491-7. doi: 10.1093/jac/dki253. Epub 2005 Jul 29.


Background: Erythromycin is the drug of choice to treat human campylobacteriosis. Campylobacter isolates exhibit two different phenotypes with regard to erythromycin resistance: high-level resistant strains (HLR) and low-level resistant strains (LLR).

Objectives: To study the mechanisms of resistance of Campylobacter to erythromycin, its 6-O-methyl derivative clarithromycin and the ketolide telithromycin.

Results: We observed a cross-resistance against these three molecules but in contrast, no cross-resistance to quinolones. Analyses of LLR showed no mutation on the 23S rDNA and the presence of a drug transport system, which can be inhibited by phenylalanine arginine beta-naphthylamide (PAbetaN), an efflux-pump inhibitor. In contrast, no PAbetaN-sensitive drug transport was identified in HLR but we found mutations in the rDNA, which were responsible for decreased binding of telithromycin to purified ribosomes. We further showed that the CmeB efflux pump already described in Campylobacter is not involved in the PAbetaN-sensitive transport of telithromycin.

Conclusions: Mutations in the ribosome confer high-level macrolide/ketolide resistance. Low-level resistance was mediated by an efflux mechanism which is sensitive to PAbetaN. This efflux pump was selective to macrolides/ketolide and was different from the previously described Campylobacter efflux pump.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Campylobacter / drug effects*
  • Campylobacter / genetics
  • Campylobacter / physiology
  • Clarithromycin / pharmacology
  • DNA, Ribosomal / drug effects
  • DNA, Ribosomal / genetics
  • Dipeptides / pharmacology
  • Drug Resistance, Multiple, Bacterial / genetics
  • Drug Resistance, Multiple, Bacterial / physiology*
  • Erythromycin / pharmacology
  • Ketolides / pharmacology
  • Macrolides / pharmacology*
  • Membrane Transport Proteins / drug effects
  • Membrane Transport Proteins / genetics
  • Microbial Sensitivity Tests
  • Mutation*


  • Anti-Bacterial Agents
  • DNA, Ribosomal
  • Dipeptides
  • Ketolides
  • Macrolides
  • Membrane Transport Proteins
  • phenylalanine arginine beta-naphthylamide
  • Erythromycin
  • Clarithromycin
  • telithromycin