JAC Advance Access published online on February 11, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg126
© 2003 by The British Society for Antimicrobial Chemotherapy
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Original article
1 Department of Molecular Virology and Microbiology, One Baylor
Plaza, Mail-stop: BCM-280,
Baylor College of Medicine, Houston, TX 77030-3411, USA
* Corresponding author. E-mail: elz{at}bcm.tmc.edu.
Received 9 April 2002
; revised 11 October 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
Relative contributions of the AcrAB, MdfA and NorE
efflux pumps
to quinolone resistance in Escherichia coli
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.
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