JAC Advance Access originally published online on July 29, 2005
Journal of Antimicrobial Chemotherapy 2005 56(3):491-497; doi:10.1093/jac/dki253
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Molecular basis of macrolide resistance in Campylobacter: role of efflux pumps and target mutations
1 Université de la Méditerranée, Enveloppe Bactérienne, Perméabilité et Antibiotiques, EA2197, IFR48, Faculté de Médecine, 27 Bd Jean Moulin 13385, Marseille Cedex 05, France; 2 Université Victor Segalen Bordeaux 2, Laboratoire de Bactériologie, Centre National de Référence des Campylobacters, Bordeaux, France
Received 18 March 2005; returned 9 May 2005; revised 24 May 2005; accepted 23 June 2005
* Corresponding author. Tel: +33-4-91-32-44-40; Fax: +33-4-91-32-46-06; E-mail: Jean-Michel.Bolla{at}medecine.univ-mrs.fr
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 ß-naphthylamide (PAßN), an efflux-pump inhibitor. In contrast, no PAßN-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 PAßN-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 PAßN. This efflux pump was selective to macrolides/ketolide and was different from the previously described Campylobacter efflux pump.
Keywords: macrolides , ketolides , efflux pumps , efflux pump inhibitors , ribosome binding
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