JAC Advance Access published online on November 1, 2002
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkf224
© 2002 by The British Society for Antimicrobial Chemotherapy
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In Brief
1 The John D. Dingell Department
of Veteran's Affairs Medical Center, Wayne State University School of
Medicine, Detroit, MI 48201, USA; Department of Internal Medicine,
Division of Infectious Diseases, Wayne State University School of
Medicine, Detroit, MI 48201, USA
* Corresponding author. E-mail: gkaatz{at}juno.com.
Received 12 June 2002
; revised 22 July 2002
; accepted 20 August 2002
Moxifloxacin is a C8-methoxy (C8-OMe) fluoroquinolone
that is highly active against Staphylococcus aureus,
including many strains resistant to older fluoroquinolones such
as ciprofloxacin. Available data indicate that it is a poor substrate
for the NorA multidrug efflux pump. We produced a mutant of S.
aureus in vitro (SA-K2068) with a novel non-NorA-mediated multidrug
resistance phenotype characterized by raised MICs of several fluoroquinolones, including
the C8-OMe fluoroquinolones, moxifloxacin and gatifloxacin, and
the organic cations ethidium and tetraphenylphosphonium. Reserpine
reduced MIC increases by two- to eight-fold. SA-K2068 also demonstrated
reduced accumulation of moxifloxacin, gatifloxacin and enoxacin, and
increased efflux of ethidium, activities that were completely blocked
by carbonyl cyanide m-chlorophenyl hydrazone
(CCCP); competition experiments indicated that a single pump was responsible
for the phenotype. The effect of CCCP and ionophores identified
the proton motive force as the source of energy for efflux. These
data, combined with previous work from our laboratory and genome
sequence data, indicate that S. aureus possesses
several multidrug efflux pump proteins and it is apparent that C8-OMe
fluoroquinolones can be substrates for such pumps.
Keywords: Staphylococcus aureus, multidrug
efflux
Identification and characterization of a novel
efflux-related multidrug resistance phenotype in Staphylococcus
aureus
2 Department of Internal Medicine,
Division of Infectious Diseases, Wayne State University School of
Medicine, Detroit, MI 48201, USA
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