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Antimicrobial Agents and Chemotherapy, December 2000, p. 3322-3327, Vol. 44, No. 12
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Substrate Specificities of MexAB-OprM, MexCD-OprJ, and MexXY-OprM Efflux Pumps in Pseudomonas aeruginosa

Nobuhisa Masuda,1,* Eiko Sakagawa,1 Satoshi Ohya,1 Naomasa Gotoh,2 Hideto Tsujimoto,2 and Takeshi Nishino2

Biological Research Laboratories, Sankyo Co., Ltd., Shinagawa-ku, Tokyo 140-8710,1 and Department of Microbiology, Kyoto Pharmaceutical University, Yamashina, Kyoto 607-8414,2 Japan

Received 28 March 2000/Returned for modification 27 June 2000/Accepted 11 September 2000

To find the exact substrate specificities of three species of tripartite efflux systems of Pseudomonas aeruginosa, MexAB-OprM, MexCD-OprJ, and MexXY-OprM, we constructed a series of isogenic mutants, each of which constitutively overproduced one of the three efflux systems and lacked the other two, and their isogenic mutants, which lacked all these systems. Comparison of the susceptibilities of the constructed mutants to 52 antimicrobial agents belonging to various groups suggested the following substrate specificities. All of the efflux systems extrude a wide variety of antimicrobial agent groups, i.e., quinolones, macrolides, tetracyclines, lincomycin, chloramphenicol, most penicillins (all but carbenicillin and sulbenicillin), most cephems (all but cefsulodin and ceftazidime), meropenem, and S-4661, but none of them extrude polymyxin B or imipenem. Extrusion of aminoglycosides is specific to MexXY-OprM, and extrusion of a group of the beta -lactams, i.e., carbenicillin, sulbenicillin, ceftazidime, moxalactam, and aztreonam, is specific to MexAB-OprM. Moreover, MexAB-OprM and MexCD-OprJ extrude novobiocin, cefsulodin, and flomoxef, while MexXY-OprM does not. These substrate specificities are distinct from those reported previously.

* Corresponding author. Present address: Department of Genetics, Warren Alpert Building, Room 513, Harvard Medical School, 200 Longwood Ave., Boston, MA 02115. Phone: (617) 432-7561. Fax: (617) 432-7266. E-mail: nmasud{at}shina.sankyo.co.jp.

Antimicrobial Agents and Chemotherapy, December 2000, p. 3322-3327, Vol. 44, No. 12
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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