Interplay between MexAB-OprM and MexEF-OprN in clinical isolates of Pseudomonas aeruginosa

Gertrudis Horna1,2, María López3, Humberto Guerra2

  • 1Barcelona Institute for Global Health, ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.

Scientific Reports
|November 9, 2018
PubMed

Insights

The study reveals how the MexEF-OprN efflux pump system influences MexAB-OprM expression in Pseudomonas aeruginosa clinical isolates, impacting antibiotic resistance. Understanding this interplay is key to developing new strategies against multidrug-resistant bacteria.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Antimicrobial Resistance Research

Background:

  • Pseudomonas aeruginosa utilizes efflux pumps like MexAB-OprM and MexEF-OprN to develop antibiotic resistance.
  • Previous research suggests the MexEF-OprN regulation system affects MexAB-OprM expression levels.

Purpose of the Study:

  • To investigate the interaction between MexAB-OprM and MexEF-OprN efflux pump systems in clinical Pseudomonas aeruginosa isolates.
  • To correlate genetic modifications in efflux pump regulators with antibiotic resistance phenotypes.

Main Methods:

  • Analysis of 90 clinical Pseudomonas aeruginosa isolates exhibiting efflux pump overexpression.
  • Identification of relevant modifications (RM) in genes including oprD, nalC, nalD, mexR, and MexS.
  • Statistical association analysis between genetic modifications and phenotypes like multidrug resistance (MDR) and carbapenem non-susceptibility.

Main Results:

  • 33% of isolates showed relevant modifications in oprD, linked to carbapenem resistance.
  • 33% displayed relevant modifications in regulators (nalC, nalD, mexR), associated with MDR, carbapenem resistance, OprD alterations, and biofilm production.
  • Modifications in MexS correlated with pigment production; however, MDR association with MexAB-OprM regulators was significant only when MexS was wild-type.

Conclusions:

  • The MexEF-OprN system modulates MexAB-OprM expression in a clinical context of Pseudomonas aeruginosa.
  • Genetic alterations in efflux pump regulators play a significant role in multidrug resistance and carbapenem resistance.
  • Targeting the interplay between these efflux pump systems could offer novel therapeutic strategies against antimicrobial resistance.

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