Journal Article

Molecular basis of macrolide resistance in <i>Campylobacter</i>: role of efflux pumps and target mutations

Laurent Mamelli, Valérie Prouzet-Mauléon, Jean-Marie Pagès, Francis Mégraud and Jean-Michel Bolla

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 56, issue 3, pages 491-497
Published in print September 2005 | ISSN: 0305-7453
Published online July 2005 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dki253
Molecular basis of macrolide resistance in Campylobacter: role of efflux pumps and target mutations

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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 β-naphthylamide (PAβN), an efflux-pump inhibitor. In contrast, no PAβN-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 PAβN-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 PAβN. 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

Journal Article.  4640 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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