Mutations in PA3574 (nalD) lead to increased MexAB-OprM expression and multidrug resistance in laboratory and clinical isolates of Pseudomonas aeruginosa

Antimicrob Agents Chemother. 2005 May;49(5):1782-6. doi: 10.1128/AAC.49.5.1782-1786.2005.

Abstract

Mutations in genes mexR and nalC have previously been shown to drive overexpression of the MexAB-OprM multidrug efflux system in Pseudomonas aeruginosa. A transposon insertion multidrug-resistant mutant of P. aeruginosa overproducing MexAB-OprM was disrupted in yet a third gene, PA3574, encoding a probable repressor of the TetR/AcrR family that we have dubbed NalD. Clinical strains overexpressing MexAB-OprM but lacking mutations in mexR or nalC were also shown to carry mutations in nalD. Moreover, the cloned nalD gene reduced the multidrug resistance and MexAB-OprM expression of the transposon mutant and clinical isolates, highlighting the significance of the nalD mutations vis-a-vis MexAB-OprM overexpression in these isolates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Outer Membrane Proteins / biosynthesis*
  • Bacterial Outer Membrane Proteins / genetics*
  • Cloning, Molecular
  • DNA Transposable Elements / genetics
  • DNA, Bacterial / genetics
  • Drug Resistance, Multiple, Bacterial
  • Electrophoresis, Polyacrylamide Gel
  • Immunoblotting
  • Membrane Transport Proteins / biosynthesis*
  • Membrane Transport Proteins / genetics*
  • Microbial Sensitivity Tests
  • Mutagenesis
  • Mutation / genetics*
  • Mutation / physiology
  • Phenotype
  • Plasmids / genetics
  • Pseudomonas Infections / microbiology*
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Bacterial Outer Membrane Proteins
  • DNA Transposable Elements
  • DNA, Bacterial
  • Membrane Transport Proteins
  • OprM protein, Pseudomonas aeruginosa