JAC Advance Access originally published online on February 11, 2003
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Journal of Antimicrobial Chemotherapy (2003) 51, 545-556
© 2003 The British Society for Antimicrobial Chemotherapy
Relative contributions of the AcrAB, MdfA and NorE efflux pumps to quinolone resistance in Escherichia coli
Department of Molecular Virology and Microbiology, One Baylor Plaza, Mail-stop: BCM-280, Baylor College of Medicine, Houston, TX 77030-3411, USA
Received 9 April 2002; returned 11 October 2002; revised 13 November 2002; accepted 16 December 2002
Quinolones are widely used, broad-spectrum antimicrobial agents. In screens for genes that, when overexpressed, allow Escherichia coli to grow on otherwise lethal concentrations of the fluoroquinolone norfloxacin, the ydhE gene was identified. We have shown that ydhE encodes a multidrug efflux pump with a narrower substrate range than that of its closest homologue, encoded by norM, and named the gene norE. The relative contributions to drug resistance of NorE compared with the two other known E. coli quinolone pumps, AcrAB and MdfA, have been defined. Overexpression of each of the three pumps separately resulted in roughly similar levels of quinolone resistance, whereas simultaneous overexpression of norE or mdfA in combination with acrAB gave synergic increases in quinolone resistance. The level of quinolone resistance mediated by efflux pumps seems to be constrained to an 
10-fold maximum, even with increased production of the pumps. We measured the drug resistance of an isogenic set of strains containing the various permutations of single, double and triple drug efflux pump mutants. The 
norE and mdfA mutants were somewhat more susceptible to fluoroquinolones than the parent strain, and acrAB mutants were four- to six-fold more susceptible. Mutants lacking two or all three efflux pumps were not significantly more susceptible to fluoroquinolones than those lacking only one of the three pumps.
* This author has previously published as Sonia Rahmati.
Corresponding author. Tel: +1-713-798-5126; Fax: +1-713-798-7375; E-mail: elz{at}bcm.tmc.edu
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