Köhler T, Kok M, Michea-Hamzehpour M, Plesiat P, Gotoh N, Nishino T, Curty L K, Pechere J C
Department of Genetics and Microbiology, Centre Médical Universitaire, Geneva, Switzerland.
Antimicrob Agents Chemother. 1996 Oct;40(10):2288-90. doi: 10.1128/AAC.40.10.2288.
Pseudomonas aeruginosa possesses at least two multiple drug efflux systems which are defined by the outer membrane proteins OprM and OprJ. We have found that mutants overexpressing OprM were two- and eightfold more resistant than their wild-type parent to sulfamethoxazole (SMX) and trimethoprim (TMP), respectively. For OprJ-overproducing strains, MICs of TMP increased fourfold but those of SMX were unchanged. Strains overexpressing OprM, but not those overexpressing OprJ, became hypersusceptible to TMP and SMX when oprM was inactivated. The wild-type antibiotic profile could be restored in an oprM mutant by transcomplementation with the cloned oprM gene. These results demonstrate that the mexABoprM multidrug efflux system is mainly responsible for the intrinsic resistance of P. aeruginosa to TMP and SMX.
铜绿假单胞菌拥有至少两种多药外排系统,它们由外膜蛋白OprM和OprJ所界定。我们发现,过表达OprM的突变体对磺胺甲恶唑(SMX)和甲氧苄啶(TMP)的抗性分别比其野生型亲本高两倍和八倍。对于过量产生OprJ的菌株,TMP的最低抑菌浓度(MIC)增加了四倍,但SMX的MIC没有变化。当过表达OprM的菌株而非过表达OprJ的菌株中的oprM失活时,它们对TMP和SMX变得高度敏感。通过用克隆的oprM基因进行反式互补,可在oprM突变体中恢复野生型抗生素谱。这些结果表明,mexABoprM多药外排系统主要负责铜绿假单胞菌对TMP和SMX的固有抗性。