High-level fluoroquinolone resistance in Pseudomonas aeruginosa due to interplay of the MexAB-OprM efflux pump and the DNA gyrase mutation

Microbiol Immunol. 2002;46(6):391-5. doi: 10.1111/j.1348-0421.2002.tb02711.x.

Abstract

Fluoroquinolone resistance in Pseudomonas aeruginosa is mainly attributable to the constitutive expression of the xenobiotic efflux pump and mutation in DNA gyrase or topoisomerase IV. We constructed cells with a double-mutation in gyrA and mexR encoding DNA gyrase and repressor for the mexAB-oprM operon, respectively. The mutant showed 1,024 times higher fluoroquinolone resistance than cells lacking the MexAB-OprM. Cells with a single mutation in gyrA and producing a wild-type level of the MexAB-OprM efflux pump showed 128 times higher fluoroquinolone resistance than cells lacking the MexAB-OprM. In contrast, a single mutation in gyrA or mexR caused only 4 and 64 times higher resistance, respectively. These findings manifested the interplay between the MexAB-OprM efflux pump and the target mutation in fluoroquinolone resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents / pharmacokinetics
  • Anti-Infective Agents / pharmacology*
  • Bacterial Outer Membrane Proteins / metabolism*
  • Bacterial Proteins*
  • Blotting, Western
  • DNA Gyrase / genetics
  • DNA Gyrase / metabolism*
  • Drug Resistance, Bacterial / genetics*
  • Fluoroquinolones
  • Gene Expression Regulation, Bacterial
  • Membrane Transport Proteins / metabolism*
  • Mutagenesis, Insertional
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / genetics
  • Pseudomonas aeruginosa / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*

Substances

  • Anti-Infective Agents
  • Bacterial Outer Membrane Proteins
  • Bacterial Proteins
  • Fluoroquinolones
  • Membrane Transport Proteins
  • MexR protein, Pseudomonas aeruginosa
  • OprM protein, Pseudomonas aeruginosa
  • Repressor Proteins
  • DNA Gyrase