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Mechanisms of Resistance

Contribution of the MexX-MexY-OprM Efflux System to Intrinsic Resistance in Pseudomonas aeruginosa

Nobuhisa Masuda, Eiko Sakagawa, Satoshi Ohya, Naomasa Gotoh, Hideto Tsujimoto, Takeshi Nishino
Nobuhisa Masuda
Biological Research Laboratories, Sankyo Co., Ltd., Shinagawa-ku, Tokyo 140-8710, 1 and
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Eiko Sakagawa
Biological Research Laboratories, Sankyo Co., Ltd., Shinagawa-ku, Tokyo 140-8710, 1 and
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Satoshi Ohya
Biological Research Laboratories, Sankyo Co., Ltd., Shinagawa-ku, Tokyo 140-8710, 1 and
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Naomasa Gotoh
Department of Microbiology, Kyoto Pharmaceutical University, Yamashina, Kyoto 607-8414, 2 Japan
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Hideto Tsujimoto
Department of Microbiology, Kyoto Pharmaceutical University, Yamashina, Kyoto 607-8414, 2 Japan
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Takeshi Nishino
Department of Microbiology, Kyoto Pharmaceutical University, Yamashina, Kyoto 607-8414, 2 Japan
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DOI: 10.1128/AAC.44.9.2242-2246.2000
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ABSTRACT

To test the possibility that MexX-MexY, a new set of efflux system components, is associated with OprM and contributes to intrinsic resistance in Pseudomonas aeruginosa, we constructed a series of isogenic mutants lacking mexXY and/ormexAB and/or oprM from a laboratory strain PAO1, and examined their susceptibilities to ofloxacin, tetracycline, erythromycin, gentamicin, and streptomycin. Loss of either MexXY or OprM from the MexAB-deficient mutant increased susceptibility to all agents tested, whereas loss of MexXY from the MexAB-OprM-deficient mutant caused no change in susceptibility. Introduction of an OprM expression plasmid decreased the susceptibility of themexAB-oprM-deficient-/mexXY-maintaining mutant, yet caused no change in the susceptibility of amexAB-oprM- and mexXY-deficient double mutant. Immunoblot analysis using anti-MexX polyclonal rabbit serum generated against synthetic oligopeptides detected expression of MexX in the PAO1 cells grown in medium containing tetracycline, erythromycin, or gentamicin, although expression of MexX was undetectable in the cells incubated in medium without any agent. These results suggest that MexXY induced by these agents is functionally associated with spontaneously expressed OprM and contributes to the intrinsic resistance to these agents.

  • Copyright © 2000 American Society for Microbiology
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Contribution of the MexX-MexY-OprM Efflux System to Intrinsic Resistance in Pseudomonas aeruginosa
Nobuhisa Masuda, Eiko Sakagawa, Satoshi Ohya, Naomasa Gotoh, Hideto Tsujimoto, Takeshi Nishino
Antimicrobial Agents and Chemotherapy Sep 2000, 44 (9) 2242-2246; DOI: 10.1128/AAC.44.9.2242-2246.2000

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Contribution of the MexX-MexY-OprM Efflux System to Intrinsic Resistance in Pseudomonas aeruginosa
Nobuhisa Masuda, Eiko Sakagawa, Satoshi Ohya, Naomasa Gotoh, Hideto Tsujimoto, Takeshi Nishino
Antimicrobial Agents and Chemotherapy Sep 2000, 44 (9) 2242-2246; DOI: 10.1128/AAC.44.9.2242-2246.2000
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