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Updated: Jun 14, 2026

Expression, Detergent Solubilization, and Purification of a Membrane Transporter, the MexB Multidrug Resistance Protein
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Changes in the expression of mexB, mexY, and oprD in clinical Pseudomonas aeruginosa isolates

Yoshimi Matsumoto1, Seiji Yamasaki1,2,3, Kouhei Hayama1

  • 1SANKEN (The Institute of Scientific and Industrial Research), Osaka University.

Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
|January 10, 2024
PubMed

Insights

Efflux pump inhibitors combined with antibiotics like ciprofloxacin or aztreonam show promise for treating multidrug-resistant Pseudomonas aeruginosa (MDRP) infections. This approach targets key genes like mexY and oprD, enhancing drug susceptibility.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Pharmacology

Background:

  • Pseudomonas aeruginosa is a significant opportunistic pathogen.
  • Multidrug resistance (MDRP) in P. aeruginosa poses a major clinical challenge.
  • Efflux pumps and porin channels are key mechanisms of antibiotic resistance.

Purpose of the Study:

  • To investigate the role of efflux pump genes (mexB, mexY) and porin gene (oprD) in MDRP.
  • To evaluate the efficacy of an efflux pump inhibitor (Phe-Arg-β-naphthylamide) in restoring antibiotic susceptibility.
  • To determine the prevalence of metallo-β-lactamase (MBL) and AAC(6')-Iae in MDRP strains.

Main Methods:

  • Comparative analysis of gene expression in MDRP, drug-sensitive, and single-antibiotic resistant strains.
  • Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) for gene expression analysis.
  • Determination of antibiotic susceptibility before and after efflux pump inhibitor treatment.

Main Results:

  • Efflux pump inhibitor treatment resensitized MDRP to ciprofloxacin (71%), aztreonam (73%), and imipenem (29%).
  • MBL and AAC(6')-Iae were prevalent in 69% and 62% of MDRP strains, respectively.
  • Elevated mexY expression (76% of strains) and reduced oprD expression (69% of strains) were observed in MDRP.

Conclusions:

  • Overexpression of mexY and underexpression of oprD are significant in MDRP.
  • Combination therapy with efflux pump inhibitors and antibiotics like ciprofloxacin or aztreonam could be a viable strategy for treating MDRP infections.
Keywords:
Phe-Arg-β-naphthylamideaminoglycoside acetyltransferasemetallo-β-lactamasemultidrug efflux pumpsmultidrug resistance

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