Structures of the wild-type MexAB-OprM tripartite pump reveal its complex formation and drug efflux mechanism

Related Experiment Video

Updated: Jan 26, 2026

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

12.2K

Kenta Tsutsumi1, Ryo Yonehara1, Etsuko Ishizaka-Ikeda1

  • 1Institute for Protein Research, Osaka University, Suita, 565-0871, Osaka, Japan.

Nature Communications
|April 5, 2019
PubMed

Insights

The MexAB-OprM pump structure in Pseudomonas aeruginosa was determined, revealing its drug efflux mechanism. This finding is crucial for understanding and combating multidrug resistance in bacterial infections.

Area of Science:

  • Microbiology
  • Structural Biology
  • Biochemistry

Background:

  • The MexAB-OprM efflux pump in *Pseudomonas aeruginosa* is a key factor in multidrug resistance.
  • This pump contributes to serious nosocomial infections by expelling various drugs.
  • Previous structural studies only solved individual components, not the fully assembled pump.

Purpose of the Study:

  • To determine the near-atomic resolution structure of the wild-type MexAB-OprM pump.
  • To elucidate the mechanisms of complex formation and drug efflux mediated by MexAB-OprM.
  • To identify key residues and conformational changes involved in pump function.

Main Methods:

  • X-ray crystallography was used to obtain high-resolution structures of the MexAB-OprM pump.
  • Structures were determined in the presence and absence of drugs.
  • Biochemical methods were employed to confirm essential residues for complex formation.

Main Results:

  • The structure reveals that OprM does not directly interact with MexB; complex formation is mediated differently.
  • A periplasmic gate in OprM opens via complex formation.
  • Movement of the drug entrance gate was observed, and essential residues for complex formation were identified.

Conclusions:

  • The study proposes novel mechanisms for MexAB-OprM complex formation and drug efflux.
  • Understanding these mechanisms can inform strategies to overcome multidrug resistance.
  • The structural insights provide a foundation for developing new antimicrobial therapies targeting efflux pumps.

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