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

Author:

Lee Angela1,Mao Weimin1,Warren Mark S.1,Mistry Anita1,Hoshino Kazuki2,Okumura Ryo2,Ishida Hiroko2,Lomovskaya Olga1

Affiliation:

1. Microcide Pharmaceuticals Inc., Mountain View, California 94043,1 and

2. Daiichi Pharmaceutical Co., Ltd., Tokyo 134, Japan2

Abstract

ABSTRACT 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.

Publisher

American Society for Microbiology

Subject

Molecular Biology,Microbiology

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