Interplay between the MexA-MexB-OprM multidrug efflux system and the outer membrane barrier in the multiple antibiotic resistance of Pseudomonas aeruginosa

J Antimicrob Chemother. 2000 Apr;45(4):433-6. doi: 10.1093/jac/45.4.433.

Abstract

MexAB-OprM is a constitutively expressed multidrug efflux system of Pseudomonas aeruginosa. Using isogenic pump mutants, the contributions of the MexAB-OprM efflux pump and the outer membrane barrier to multiple antibiotic resistance were evaluated by assessing the influence of pump inactivation and outer membrane permeabilization on antibiotic susceptibility. Both pump inactivation and increased outer membrane permeability enhanced antibiotic susceptibility, although maximal susceptibility was achieved when the two were combined. Thus, inhibition of antibiotic efflux pumps and permeabilization of the outer membrane constitute an effective approach to reversing the antibiotic resistance of this organism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Membrane Permeability / drug effects
  • Drug Resistance, Multiple / genetics
  • Drug Resistance, Multiple / physiology*
  • Edetic Acid / pharmacology
  • Genes, Bacterial / genetics*
  • Membrane Transport Proteins*
  • Microbial Sensitivity Tests
  • Phosphates / pharmacology
  • Pseudomonas aeruginosa / metabolism*

Substances

  • Bacterial Outer Membrane Proteins
  • Carrier Proteins
  • Membrane Transport Proteins
  • MexA protein, Pseudomonas aeruginosa
  • MexB protein, Pseudomonas aeruginosa
  • OprM protein, Pseudomonas aeruginosa
  • Phosphates
  • Edetic Acid
  • sodium polymetaphosphate