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Antimicrobial Agents and Chemotherapy, April 2001, p. 1126-1136, Vol. 45, No. 4
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.4.1126-1136.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Antibiotic Susceptibility Profiles of Escherichia coli Strains Lacking Multidrug Efflux Pump Genes

Mark C. Sulavik,1,* Chad Houseweart,1 Christina Cramer,2 Nilofer Jiwani,1,dagger Nicholas Murgolo,2 Jonathan Greene,2 Beth DiDomenico,2 Karen Joy Shaw,2,Dagger George H. Miller,2,§ Roberta Hare,2 and George Shimer1,||

Genome Therapeutics Corporation, Waltham, Massachusetts,1 and Schering-Plough Research Institute, Kenilworth, New Jersey2

Received 10 October 2000/Returned for modification 19 November 2000/Accepted 18 January 2001

The contribution of seven known and nine predicted genes or operons associated with multidrug resistance to the susceptibility of Escherichia coli W3110 was assessed for 20 different classes of antimicrobial compounds that include antibiotics, antiseptics, detergents, and dyes. Strains were constructed with deletions for genes in the major facilitator superfamily, the resistance nodulation-cell division family, the small multidrug resistance family, the ATP-binding cassette family, and outer membrane factors. The agar dilution MICs of 35 compounds were determined for strains with deletions for multidrug resistance (MDR) pumps. Deletions in acrAB or tolC resulted in increased susceptibilities to the majority of compounds tested. The remaining MDR pump gene deletions resulted in increased susceptibilities to far fewer compounds. The results identify which MDR pumps contribute to intrinsic resistance under the conditions tested and supply practical information useful for designing sensitive assay strains for cell-based screening of antibacterial compounds.

* Corresponding author. Present address: Cubist Pharmaceuticals, 24 Emily St., Cambridge, MA 02139. Phone: (617) 576-4224. Fax: (617) 576-0232. E-mail: msulavik{at}cubist.com.

dagger Present address: Aventis Pharmaceuticals, Bridgewater, N.J.

Dagger Present address: R. W. Johnson Pharmaceutical Research Institute, San Diego, Calif.

§ Present address: Microcide Pharmaceuticals, Inc., Mountain View, Calif.

|| Present address: Cubist Pharmaceuticals, Inc., Cambridge, Mass.

Antimicrobial Agents and Chemotherapy, April 2001, p. 1126-1136, Vol. 45, No. 4
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.4.1126-1136.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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