Skip Navigation


JAC Advance Access originally published online on March 6, 2009
Journal of Antimicrobial Chemotherapy 2009 63(5):909-916; doi:10.1093/jac/dkp054
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
63/5/909    most recent
dkp054v1
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 Ricci, V.
Right arrow Articles by Piddock, L. J. V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ricci, V.
Right arrow Articles by Piddock, L. J. V.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2009. 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

Original research

Ciprofloxacin selects for multidrug resistance in Salmonella enterica serovar Typhimurium mediated by at least two different pathways

Vito Ricci and Laura J. V. Piddock*

Antimicrobial Agents Research Group, School of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, UK

Received 3 December 2008; returned 6 January 2009; revised 21 January 2009; accepted 30 January 2009

* Corresponding author. Tel: +44-121-414-6966; Fax: +44-121-414-6815; E-mail: l.j.v.piddock{at}bham.ac.uk

Objectives: The aim of this study was to understand the role of ramA in conferring multidrug resistance (MDR) in Salmonella enterica serovar Typhimurium.

Methods: Two phenotypically distinct isogenic MDR laboratory mutants derived from Salmonella Typhimurium SL1344 and three human clinical isolates from a patient that failed antibiotic therapy, including with ciprofloxacin, were investigated for the cause of MDR. MICs were determined by agar dilution and efflux activity assessed by monitoring the accumulation of Hoechst 33342. The combination of specific genes and MDR was assessed by inactivation, and complementation RT–PCR was used to assess gene expression and DNA sequencing to identify mutations within genes of interest.

Results: Mutation in ramR and the consequent over-production of ramA and acrB were revealed in one laboratory mutant selected with ciprofloxacin and this was associated with cyclohexane tolerance. Complementation of SL1344 ramR::aph with pUC19 ramRmutant conferred MDR and cyclohexane tolerance. However, analysis of a second ciprofloxacin-selected MDR mutant, which was susceptible to cyclohexane, revealed no mutation in ramR or altered expression of marA, soxS or rob. There was a mutation in ramR in both the pre- and post-therapy clinical isolates and no difference between the isolates in the level of expression of ramA.

Conclusions: These data show that ciprofloxacin exposure can select for mutations within ramR and consequently mediate MDR. These data also indicate that there is at least one further unidentified gene in addition to marA, soxS, rob and ramA that confers MDR in S. enterica.

Keywords: MDR , ramA , ramR


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




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.