We have obtained the following results in the investigation of multidrug efflux systems in which endow multidrug resistance in Pseudomonas aeruginosa.
1. The three multidrug efflux operons, mexA-mexB-oprM,mexC-mexD-oprJ and mexE-mexF-opeN,were encoded on the chromosome of P.aeruginosa.
2. Expression of mexC-mexD-oprJ is negatively regulated by the nfxBgene, whereas that of mexE-mexF-opeN is stimulated by the nfxC gene.
3. Substrate profiles of multidrug efflux systems are distinguishable to each others.
These results showed that multidrug resistasnce in P.aeruginosa is caused at least by expression of the identified three efflux operons.
Moreover, characterization of the identified multidrug efflux systems informed the followings.
1. THe mexA-mexB-oprM multidrug efflux system is mainly responsible for the intrinsic resistance of P.aeruginosa to trimethoprim and sulfamethoxazole as well as fluoroquinolones, cephems, tetracyline and chloramphenicol.
2. There are at least two nfxB mutations that show different phenotypes and that production of OprJ is associated with changes in susceptibilities of nfxB mutation.
3. Deficiency of OprJ from the MexC-MexD-OprJ system by insertion mutagenesis was functionally complemented by the homologous outer membrane protein OprM.
Taken together, the outer membrane proteins, OprM,OprJ and OprN,which are composed of the efflux systems, function as stimulators, but not as main pumps.