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JAC Advance Access originally published online on September 12, 2005
Journal of Antimicrobial Chemotherapy 2005 56(5):948-950; doi:10.1093/jac/dki292
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Published by Oxford University Press 2005

Involvement of the CmeABC efflux pump in the macrolide resistance of Campylobacter coli

Cédric Cagliero, Christian Mouline, Sophie Payot* and Axel Cloeckaert

Institut National de la Recherche Agronomique, UR086 BioAgresseurs, Santé, Environnement, 37380 Nouzilly, France

Received 6 June 2005; returned 20 June 2005; revised 26 July 2005; accepted 27 July 2005

* Corresponding author. Tel: +33-2-47-42-79-88; Fax: +33-2-47-42-77-74; E-mail: payot{at}tours.inra.fr

Objectives: 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.

Keywords: transporters , gene inactivation , mutations , 23S rRNA , ketolides


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