Skip Navigation



JAC Advance Access published online on October 5, 2006
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl412
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
58/6/1154    most recent
dkl412v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Yan, M.
Right arrow Articles by Zhang, Q.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yan, M.
Right arrow Articles by Zhang, Q.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Received June 23, 2006
Revised September 14, 2006
Accepted September 14, 2006

Original article

Role of the CmeABC efflux pump in the emergence of fluoroquinolone-resistant Campylobacter under selection pressure

Meiguan Yan 1, Orhan Sahin 1, Jun Lin 1 {dagger}, and Qijing Zhang 1 *

1 Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA

* To whom correspondence should be addressed.
Qijing Zhang, E-mail: zhang123{at}iastate.edu


  Abstract

Objectives: The objective of this study was to determine the contribution of the CmeABC efflux pump to the emergence of fluoroquinolone (FQ)-resistant mutants in Campylobacter jejuni under various levels of selection pressure.

Methods: The frequency of emergence of ciprofloxacin-resistant mutants was measured in wild-type C. jejuni NCTC 11168 and its isogenic cmeB mutant and cmeR mutant (overexpressing cmeABC) using plates containing various concentrations of ciprofloxacin. Representative ciprofloxacin-resistant mutants were selected for gyrA sequence analysis and MIC determination. Accumulation of ciprofloxacin in Campylobacter cells was measured using spectrofluorometry.

Results: Mutation of cmeB drastically reduced the frequency of emergence of FQ-resistant mutants at 10x and 32x the MIC of ciprofloxacin, while the cmeR mutant displayed an approximately 17-fold increase in the frequency of emergence of the mutants at 32x the MIC when compared with the wild-type strain. Various point mutations occurred in gyrA in the FQ-resistant mutants selected at 5x and 10x the MIC, while the Thr-86->Ile mutation was predominant in the mutants selected at 32x the MIC. The Thr-86->Ile change conferred a high-level resistance to FQs, but other mutations only conferred an intermediate-level FQ resistance. In contrast, all types of gyrA mutations in the CmeABC-overexpressed background conferred high-level resistance to ciprofloxacin. Overexpression of cmeABC significantly reduced the amount of ciprofloxacin accumulated within bacterial cells.

Conclusions: CmeABC is not only important for maintaining high-level resistance to FQs but also contributes significantly to the emergence of FQ-resistant mutants. Inhibition of this efflux pump may prevent the emergence of clinically relevant FQ-resistant Campylobacter mutants.

Keywords: ciprofloxacin; gyrA mutations; efflux; antibiotic resistance.
{dagger}Present address. Department of Animal Science, University of Tennessee, Knoxville, TN 37996, USA
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Antimicrob. Agents Chemother.Home page
B. Jeon, W. Muraoka, O. Sahin, and Q. Zhang
Role of Cj1211 in Natural Transformation and Transfer of Antibiotic Resistance Determinants in Campylobacter jejuni
Antimicrob. Agents Chemother., August 1, 2008; 52(8): 2699 - 2708.
[Abstract] [Full Text] [PDF]

Home page
 J Antimicrob ChemotherHome page
M.-L. Hanninen and M. Hannula
Spontaneous mutation frequency and emergence of ciprofloxacin resistance in Campylobacter jejuni and Campylobacter coli
J. Antimicrob. Chemother., December 1, 2007; 60(6): 1251 - 1257.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
B. Jeon and Q. Zhang
Cj0011c, a Periplasmic Single- and Double-Stranded DNA-Binding Protein, Contributes to Natural Transformation in Campylobacter jejuni
J. Bacteriol., October 15, 2007; 189(20): 7399 - 7407.
[Abstract] [Full Text] [PDF]

Home page
 J Antimicrob ChemotherHome page
A. Mahamoud, J. Chevalier, S. Alibert-Franco, W. V. Kern, and J.-M. Pages
Antibiotic efflux pumps in Gram-negative bacteria: the inhibitor response strategy
J. Antimicrob. Chemother., June 1, 2007; 59(6): 1223 - 1229.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
J. Lin, M. Yan, O. Sahin, S. Pereira, Y.-J. Chang, and Q. Zhang
Effect of Macrolide Usage on Emergence of Erythromycin-Resistant Campylobacter Isolates in Chickens
Antimicrob. Agents Chemother., May 1, 2007; 51(5): 1678 - 1686.
[Abstract] [Full Text] [PDF]

Home page
 J Antimicrob ChemotherHome page
L. Mamelli, E. Demoulin, V. Prouzet-Mauleon, F. Megraud, J.-M. Pages, and J.-M. Bolla
Prevalence of efflux activity in low-level macrolide-resistant Campylobacter species
J. Antimicrob. Chemother., February 1, 2007; 59(2): 327 - 328.
[Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.