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In vitro Investigation of the MexAB Efflux Pump From Pseudomonas aeruginosa
13:40

In vitro Investigation of the MexAB Efflux Pump From Pseudomonas aeruginosa

Published on: February 17, 2014

Efflux pump inhibitors reduce the invasiveness of Pseudomonas aeruginosa

Yoichi Hirakata1, Akira Kondo, Kazuki Hoshino

  • 1Department of Infection Control and Laboratory Diagnostics, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai 980-8574, Japan. hiraichi@mail.tains.tohoku.ac.jp

International Journal of Antimicrobial Agents
|July 21, 2009
PubMed

Insights

Efflux pump inhibitors (EPIs) reduce Pseudomonas aeruginosa invasion of host cells. Specific EPIs targeting the MexAB-OprM system show promise in combating antimicrobial resistance and infection.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Infectious Diseases

Background:

  • Efflux systems, particularly MexAB-OprM, are implicated in antimicrobial resistance in Pseudomonas aeruginosa.
  • A mexAB-oprM deletion strain exhibits reduced invasion capacity in Madin-Darby canine kidney (MDCK) cells, suggesting MexAB-OprM exports invasion factors.

Purpose of the Study:

  • To investigate the effect of efflux pump inhibitors (EPIs) on the invasiveness of wild-type (WT) and MexAB-OprM-overproducing (nalB) P. aeruginosa strains.
  • To compare the efficacy of a broad-spectrum EPI (PAbetaN) and a MexAB-OprM-specific EPI (D13-9001) in inhibiting bacterial invasion.

Main Methods:

  • Treatment of P. aeruginosa PAO1 WT and nalB strains with varying concentrations of Phe-Arg-beta-naphthylamide (PAbetaN) and D13-9001.
  • Assessment of bacterial invasiveness into Madin-Darby canine kidney (MDCK) cells in the presence of EPIs.

Main Results:

  • Bacterial invasiveness was inhibited by both EPIs in a concentration-dependent manner for both WT and nalB strains.
  • The MexAB-OprM-specific EPI, D13-9001, demonstrated greater inhibition of invasiveness compared to the broad-spectrum EPI, PAbetaN.

Conclusions:

  • Efflux pump inhibitors can effectively reduce the invasiveness of P. aeruginosa.
  • EPIs, especially those targeting specific efflux systems like MexAB-OprM, hold potential as novel anti-infective agents to combat P. aeruginosa infections and resistance.

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