Changes in the expression of <i>mexB</i>, <i>mexY</i>, and <i>oprD</i> in clinical <i>Pseudomonas aeruginosa</i> isolates

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  • MATSUMOTO Yoshimi
    SANKEN (The Institute of Scientific and Industrial Research), Osaka University
  • YAMASAKI Seiji
    SANKEN (The Institute of Scientific and Industrial Research), Osaka University Graduate School of Pharmaceutical Sciences, Osaka University Institute for Advanced Co-Creation Studies, Osaka University
  • HAYAMA Kouhei
    SANKEN (The Institute of Scientific and Industrial Research), Osaka University
  • IINO Ryota
    Institute for Molecular Science, National Institutes of Natural Sciences Graduate Institute for Advanced Studies, The Graduate University for Advanced Studies (SOKENDAI)
  • NOJI Hiroyuki
    Graduate School of Engineering, The University of Tokyo
  • YAMAGUCHI Akihito
    SANKEN (The Institute of Scientific and Industrial Research), Osaka University
  • NISHINO Kunihiko
    SANKEN (The Institute of Scientific and Industrial Research), Osaka University Graduate School of Pharmaceutical Sciences, Osaka University Center for Infectious Disease Education and Research, Osaka University

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  • Changes in the expression of mexB, mexY, and oprD in clinical Pseudomonas aeruginosa isolates

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Abstract

<p>Changes in expression levels of drug efflux pump genes, mexB and mexY, and porin gene oprD in Pseudomonas aeruginosa were investigated in this study. Fifty-five multidrug-resistant P. aeruginosa (MDRP) strains were compared with 26 drug-sensitive strains and 21 strains resistant to a single antibiotic. The effect of the efflux inhibitor Phe-Arg-β-naphthylamide on drug susceptibility was determined, and gene expression was quantified using real-time quantitative real-time reverse transcription polymerase chain reaction. In addition, the levels of metallo-β-lactamase (MBL) and 6′-N-aminoglycoside acetyltransferase [AAC(6′)-Iae] were investigated. Efflux pump inhibitor treatment increased the sensitivity to ciprofloxacin, aztreonam, and imipenem in 71%, 73%, and 29% of MDRPs, respectively. MBL and AAC(6′)-Iae were detected in 38 (69%) and 34 (62%) MDRP strains, respectively. Meanwhile, 76% of MDRP strains exhibited more than 8-fold higher mexY expression than the reference strain PAO1. Furthermore, 69% of MDRP strains expressed oprD at levels less than 0.01-fold of those in PAO1. These findings indicated that efflux pump inhibitors in combination with ciprofloxacin or aztreonam might aid in treating MDRP infections.</p>

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