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Antimicrobial Agents and Chemotherapy, January 2006, p. 38-42, Vol. 50, No. 1
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.1.38-42.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Ciprofloxacin-Resistant Salmonella enterica Serovar Typhimurium Strains Are Difficult To Select in the Absence of AcrB and TolC

Vito Ricci,1 Peter Tzakas,1 Anthony Buckley,1 Nick C. Coldham,2 and Laura J. V. Piddock1*

Antimicrobial Agents Research Group, Division of Immunity and Infection, University of Birmingham, Birmingham B15 2TT,1 Department of Bacteriological Disease, Veterinary Laboratories Agency (Weybridge), New Haw, Addlestone, Surrey KT15 3NB, United Kingdom2

Received 13 May 2005/ Returned for modification 20 June 2005/ Accepted 29 October 2005

It has been proposed that lack of a functional efflux system(s) will lead to a lower frequency of selection of resistance to fluoroquinolones and other antibiotics. We constructed five strains of Salmonella enterica serovar Typhimurium SL1344 that lacked efflux gene components of resistance nodulation cell division pumps (acrB, acrD, acrF, acrBacrF, and tolC) plus three strains that lack genes that effect efflux gene expression (marA, soxS, and ramA) and a hypermutable strain (mutS::aph). Strains were exposed to ciprofloxacin at 2x the MIC in agar, in the presence and absence of Phe-Arg-ß-naphthylamide, an efflux pump inhibitor. Mutants were selected from all strains except those lacking acrB, tolC, or acrBacrF. For strains from which mutants were selected, there were no significant differences between the frequencies of resistance. Except for mutants of the ramA::aph strain, two phenotypes arose: resistance to quinolones only and multiple antibiotic resistance (MAR). ramA::aph mutants were resistant to quinolones only, suggesting a role for ramA in MAR in S. enterica serovar Typhimurium. Phe-Arg-ß-naphthylamide (20 µg/ml) had no effect on the frequencies of resistance or ciprofloxacin MICs. In conclusion, functional AcrB and TolC in S. enterica serovar Typhimurium are important for the selection of ciprofloxacin-resistant mutants.

* Corresponding author. Mailing address: Antimicrobial Agents Research Group, Division of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom. Phone: 44 121 414 6966. Fax: 44 121 414 6815. E-mail: l.j.v.piddock{at}bham.ac.uk.

Antimicrobial Agents and Chemotherapy, January 2006, p. 38-42, Vol. 50, No. 1
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.1.38-42.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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