Masuda N, Sakagawa E, Ohya S, Gotoh N, Tsujimoto H, Nishino T
Biological Research Laboratories, Sankyo Co., Ltd., Shinagawa-ku, Tokyo 140-8710, Japan.
Antimicrob Agents Chemother. 2000 Dec;44(12):3322-7. doi: 10.1128/AAC.44.12.3322-3327.2000.
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.
为了确定铜绿假单胞菌的三种三联外排系统MexAB - OprM、MexCD - OprJ和MexXY - OprM的确切底物特异性，我们构建了一系列同基因突变体，每个突变体组成型过量表达这三种外排系统中的一种且缺失另外两种，以及它们缺失所有这些系统的同基因突变体。比较构建的突变体对52种属于不同类别的抗菌剂的敏感性，提示了以下底物特异性。所有外排系统都能排出多种抗菌剂类别，即喹诺酮类、大环内酯类、四环素类、林可霉素、氯霉素、大多数青霉素（除羧苄西林和磺苄西林外）、大多数头孢菌素（除磺苄头孢菌素和头孢他啶外）、美罗培南和S - 4661，但它们都不能排出多粘菌素B或亚胺培南。氨基糖苷类的排出特异性地针对MexXY - OprM，而一组β - 内酰胺类，即羧苄西林、磺苄西林、头孢他啶、莫拉维酸和氨曲南的排出特异性地针对MexAB - OprM。此外，MexAB - OprM和MexCD - OprJ能排出新生霉素、磺苄头孢菌素和氟氧头孢，而MexXY - OprM则不能。这些底物特异性与先前报道的不同。
