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Updated: May 16, 2026

In vitro Investigation of the MexAB Efflux Pump From Pseudomonas aeruginosa
Published on: February 17, 2014
MexXY multidrug efflux system of Pseudomonas aeruginosa
Yuji Morita1, Junko Tomida, Yoshiaki Kawamura
1Department of Microbiology, School of Pharmacy, Aichi Gakuin University Nagoya, Japan.
Abstract:
Anti-pseudomonas aminoglycosides, such as amikacin and tobramycin, are used in the treatment of Pseudomonas aeruginosa infections. However, their use is linked to the development of resistance. During the last decade, the MexXY multidrug efflux system has been comprehensively studied, and numerous reports of laboratory and clinical isolates have been published. This system has been increasingly recognized as one of the primary determinants of aminoglycoside resistance in P. aeruginosa. In P. aeruginosa cystic fibrosis isolates, upregulation of the pump is considered the most common mechanism of aminoglycoside resistance. Non-fermentative Gram-negative pathogens possessing very close MexXY orthologs such as Achromobacter xylosoxidans and various Burkholderia species (e.g., Burkholderia pseudomallei and B. cepacia complexes), but not B. gladioli, are intrinsically resistant to aminoglycosides. Here, we summarize the properties (e.g., discovery, mechanism, gene expression, clinical significance) of the P. aeruginosa MexXY pump and other aminoglycoside efflux pumps such as AcrD of Escherichia coli, AmrAB-OprA of B. pseudomallei, and AdeABC of Acinetobacter baumannii. MexXY inducibility of the PA5471 gene product, which is dependent on ribosome inhibition or oxidative stress, is noteworthy. Moreover, the discovery of the cognate outer membrane component (OprA) of MexXY in the multidrug-resistant clinical isolate PA7, serotype O12 deserves special attention.
Insights
The MexXY efflux pump is a key factor in Pseudomonas aeruginosa aminoglycoside resistance, particularly in cystic fibrosis infections. Understanding its properties and related pumps is crucial for combating drug resistance in Gram-negative pathogens.
Area of Science:
- Microbiology
- Molecular Biology
- Pharmacology
Background:
- Aminoglycosides like amikacin and tobramycin are vital for treating Pseudomonas aeruginosa infections.
- Increasing aminoglycoside resistance in P. aeruginosa, especially in cystic fibrosis patients, necessitates understanding resistance mechanisms.
- The MexXY multidrug efflux system is a primary determinant of aminoglycoside resistance in P. aeruginosa.
Purpose of the Study:
- To comprehensively review the properties of the Pseudomonas aeruginosa MexXY efflux pump.
- To explore the role of MexXY and other aminoglycoside efflux pumps in Gram-negative pathogens.
- To highlight the clinical significance and mechanisms of MexXY-mediated aminoglycoside resistance.
Main Methods:
- Literature review of studies on MexXY and related efflux pumps.
- Analysis of gene expression, mechanisms, and clinical relevance of efflux systems.
- Examination of intrinsic aminoglycoside resistance in related bacterial species.
Main Results:
- MexXY is a major cause of aminoglycoside resistance in P. aeruginosa, often upregulated in cystic fibrosis isolates.
- Orthologs of MexXY confer intrinsic aminoglycoside resistance in pathogens like Achromobacter xylosoxidans and Burkholderia species.
- Other significant aminoglycoside efflux pumps include AcrD (E. coli), AmrAB-OprA (B. pseudomallei), and AdeABC (A. baumannii).
Conclusions:
- The MexXY efflux system is a critical target for overcoming aminoglycoside resistance in P. aeruginosa.
- Understanding diverse efflux pump systems is essential for developing strategies against multidrug-resistant Gram-negative bacteria.
- Further research into MexXY inducibility and its outer membrane component (OprA) may reveal new therapeutic avenues.
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