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Updated: Feb 2, 2026

In vitro Investigation of the MexAB Efflux Pump From Pseudomonas aeruginosa
Published on: February 17, 2014
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.
Abstract:
MexAB-OprM and MexEF-OprN are Pseudomonas aeruginosa efflux pumps involved in the development of antibiotic resistance. Several studies developed with laboratory strains or using a few clinical isolates have reported that the regulation system of MexEF-OprN is involved in the final levels of MexAB-OprM expression. Therefore, this study was aimed to determine the interplay between MexAB-OprM and MexEF-OprN in 90 out of 190 P. aeruginosa clinical isolates with an efflux pump overexpression phenotype. Regarding oprD, 33% (30/90) of isolates displayed relevant modifications (RM) defined as frameshift or premature stop, both related to carbapenem resistance. On the other hand, 33% of the isolates displayed RM in nalC, nalD or mexR, which were significantly associated with multidrug resistance (MDR), non-susceptibility to carbapenems, OprD alterations and strong biofilm production. Meanwhile, the RM in MexS were associated with presence of pigment (p = 0.004). Otherwise, when all the regulators were analysed together, the association between RM in MexAB-OprM regulators and MDR was only significant (p = 0.039) when mexS was the wild type. These data show the modulatory effect of MexEF-OprN on MexAB-OprM in a clinical population of P. aeruginosa. Further studies may contribute to design of novel molecules acting on this interplay to fight against antimicrobial resistance.
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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