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KmrA multidrug efflux pump from Klebsiella pneumoniae

Wakano Ogawa1, Motohiro Koterasawa, Teruo Kuroda

  • 1Department of Molecular Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Tsushima, Japan.

Biological & Pharmaceutical Bulletin
|March 2, 2006
PubMed

Insights

Researchers identified the kmrA gene in Klebsiella pneumoniae, conferring multidrug resistance. This gene

Area of Science:

  • Microbiology
  • Molecular Biology
  • Genetics

Background:

  • Multidrug resistance (MDR) is a significant challenge in treating bacterial infections.
  • Klebsiella pneumoniae is an opportunistic pathogen known for its resistance mechanisms.
  • Understanding the genetic basis of MDR is crucial for developing new therapeutic strategies.

Purpose of the Study:

  • To clone and characterize a novel gene responsible for multidrug resistance in Klebsiella pneumoniae.
  • To investigate the functional role of the cloned gene in conferring resistance to various antimicrobial agents.
  • To compare the identified gene with a known resistance gene from Salmonella enterica.

Main Methods:

  • Cloning of the kmrA gene from Klebsiella pneumoniae MGH78578 chromosomal DNA.
  • Heterologous expression of the kmrA gene in drug-hypersensitive Escherichia coli KAM32.
  • Determination of drug resistance profiles and analysis of ethidium efflux in transformed E. coli cells.
  • Cloning and characterization of the smvA gene from Salmonella enterica sv. Typhimurium LT2.

Main Results:

  • The cloned gene, designated kmrA, was successfully isolated from Klebsiella pneumoniae.
  • Expression of kmrA in E. coli conferred resistance to acriflavine, DAPI, Hoechst 33342, TPPCl, methyl viologen, and ethidium bromide.
  • Elevated energy-dependent efflux of ethidium was observed in E. coli cells expressing kmrA.
  • The deduced amino acid sequence of KmrA showed similarity to SmvA from Salmonella enterica, and both genes conferred similar resistance patterns.

Conclusions:

  • The kmrA gene from Klebsiella pneumoniae is a functional multidrug resistance determinant.
  • KmrA mediates resistance likely through an energy-dependent efflux mechanism.
  • KmrA represents a conserved mechanism of multidrug resistance across different bacterial species.

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