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Journal of Bacteriology, June 2000, p. 3142-3150, Vol. 182, No. 11
0021-9193/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Interplay between Efflux Pumps May Provide Either Additive or Multiplicative Effects on Drug Resistance

Angela Lee,1 Weimin Mao,1 Mark S. Warren,1 Anita Mistry,1 Kazuki Hoshino,2 Ryo Okumura,2 Hiroko Ishida,2 and Olga Lomovskaya1,*

Microcide Pharmaceuticals Inc., Mountain View, California 94043,1 and Daiichi Pharmaceutical Co., Ltd., Tokyo 134, Japan2

Received 13 December 1999/Accepted 5 March 2000

The effects of simultaneous expression of several efflux pumps on antibiotic resistance were investigated in Escherichia coli and Pseudomonas aeruginosa. Several combinations of efflux pumps have been studied: (i) simultaneous expression of a single-component efflux pump, which exports antibiotics into the periplasm, in combination with a multicomponent efflux pump that accomplishes efflux directly into the external medium; (ii) simultaneous expression of two single-component pumps; and (iii) simultaneous expression of two multicomponent pumps. It was found that when efflux pumps of different structural types were combined in the same cell (the first case), the observed antibiotic resistance was much higher than that conferred by each of the pumps expressed singly. Simultaneous expression of pairs of single-component or multicomponent efflux pumps (the second and third cases) did not produce strong increases in antibiotic resistance.

* Corresponding author. Mailing address: Microcide Pharmaceuticals Inc., 850 Maude Ave., Mountain View, CA 94043. Phone: (650) 428-3548. Fax: (650) 428-3550. E-mail: olga{at}microcide.com.

Journal of Bacteriology, June 2000, p. 3142-3150, Vol. 182, No. 11
0021-9193/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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