title: Interplay between efflux pumps may provide either additive or multiplicative effects on drug resistance.
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.
authors.affiliation: Microcide Pharmaceuticals Inc., Mountain View, California 94043, USA.
authors.forename: A
authors.initials: A
authors.lastname: Lee
authors.forename: W
authors.initials: W
authors.lastname: Mao
authors.forename: M S
authors.initials: MS
authors.lastname: Warren
authors.forename: A
authors.initials: A
authors.lastname: Mistry
authors.forename: K
authors.initials: K
authors.lastname: Hoshino
authors.forename: R
authors.initials: R
authors.lastname: Okumura
authors.forename: H
authors.initials: H
authors.lastname: Ishida
authors.forename: O
authors.initials: O
authors.lastname: Lomovskaya
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D002702:Chloramphenicol Resistance / Q000502:physiology; D018432:Drug Resistance, Multiple / Q000502:physiology*; D004926:Escherichia coli / Q000187:drug effects*; D008954:Models, Biological; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013753:Tetracycline Resistance / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins