Characterization of the MexC-MexD-OprJ multidrug efflux system in δmexA-mexB-oprM mutants of Pseudomonas aeruginosa

Naomasa Gotoh, Hideto Tsujimoto, Masataka Tsuda, Kiyomi Okamoto, Atsuko Nomura, Takaomi Wada, Masaaki Nakahashi, Takeshi Nishino

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    90 Citations (Scopus)

    Abstract

    Expression of the multidrug efflux system MexC-MexD-OprJ in nfxB mutants of Pseudomonas aeruginosa contributes to resistance to fluoroquinolones and the 'fourth-generation' cephems (cefpirome and cefozopran), but not to most β-lactams, including the ordinary cephems (ceftazidime and cefoperazone). nfxB mutants also express a second multidrug efflux system, MexA-MexB-OprM, due to incomplete transcriptional repression of this operon by the mexR gene product. To characterize the contribution of the MexC-MexD-OprJ system to drug resistance in P. aeruginosa, a site-specific deletion method was employed to remove the mexA-mexB-oprM region from the chromosome of wild- type and nfxB strains of P. aeruginosa. Characterization of mutants lacking the mexA-mexB-oprM region clearly indicated that the MexC-MexD-OprJ efflux system is involved in resistance to the ordinary cephems as well as fluoroquinolones and the fourth-generation cephems but not to carbenicillin and aztreonam. Rabbit polyclonal antisera and murine monoclonal antibody against the components of the MexA-MexB-OprM system were prepared and used to demonstrate the reduced production of this efflux system in the nfxB mutants. Consistent with this, transcription of the mexA-mexB-oprM operon decreased in an nfxB mutant. This reduction appears to explain the hypersusceptibility of the nfxB mutant to β-lactams, including ordinary cephems.

    Original languageEnglish
    Pages (from-to)1938-1943
    Number of pages6
    JournalAntimicrobial agents and chemotherapy
    Volume42
    Issue number8
    DOIs
    Publication statusPublished - 1998 Aug

    ASJC Scopus subject areas

    • Pharmacology
    • Pharmacology (medical)
    • Infectious Diseases

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