Properties of AdeABC and AdeIJK efflux systems of Acinetobacter baumannii compared with those of the AcrAB-TolC system of Escherichia coli

Antimicrob Agents Chemother. 2014 Dec;58(12):7250-7. doi: 10.1128/AAC.03728-14. Epub 2014 Sep 22.

Abstract

Acinetobacter baumannii contains RND-family efflux systems AdeABC and AdeIJK, which pump out a wide range of antimicrobial compounds, as judged from the MIC changes occurring upon deletion of the responsible genes. However, these studies may miss changes because of the high backgrounds generated by the remaining pumps and by β-lactamases, and it is unclear how the activities of these pumps compare quantitatively with those of the well-studied AcrAB-TolC system of Escherichia coli. We expressed adeABC and adeIJK of A. baumannii, as well as E. coli acrAB, in an E. coli host from which acrAB was deleted. The A. baumannii pumps were functional in E. coli, and the MIC changes that were observed largely confirmed the substrate range already reported, with important differences. Thus, the AdeABC system pumped out all β-lactams, an activity that was often missed in deletion studies. When the expression level of the pump genes was adjusted to a similar level for a comparison with AcrAB-TolC, we found that both A. baumannii efflux systems pumped out a wide range of compounds, but AdeABC was less effective than AcrAB-TolC in the extrusion of lipophilic β-lactams, novobiocin, and ethidium bromide, although it was more effective at tetracycline efflux. AdeIJK was remarkably more effective than a similar level of AcrAB-TolC in the efflux of β-lactams, novobiocin, and ethidium bromide, although it was less so in the efflux of erythromycin. These results thus allow us to compare these efflux systems on a quantitative basis, if we can assume that the heterologous systems are fully functional in the E. coli host.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Intramural

MeSH terms

  • Acinetobacter baumannii / drug effects
  • Acinetobacter baumannii / genetics*
  • Acinetobacter baumannii / metabolism
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / metabolism
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Drug Resistance, Multiple, Bacterial
  • Erythromycin / pharmacology
  • Escherichia coli / drug effects
  • Escherichia coli / genetics*
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / genetics*
  • Escherichia coli Proteins / metabolism
  • Ethidium / pharmacology
  • Gene Expression Regulation, Bacterial*
  • Genetic Complementation Test
  • Lipoproteins / genetics*
  • Lipoproteins / metabolism
  • Membrane Transport Proteins / genetics*
  • Membrane Transport Proteins / metabolism
  • Microbial Sensitivity Tests
  • Multidrug Resistance-Associated Proteins / genetics*
  • Multidrug Resistance-Associated Proteins / metabolism
  • Novobiocin / pharmacology
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Tetracycline / pharmacology
  • beta-Lactamases / genetics
  • beta-Lactamases / metabolism
  • beta-Lactams / pharmacology

Substances

  • AcrA protein, E coli
  • AcrB protein, E coli
  • AdeA protein, Acinetobacter baumannii
  • AdeB protein, Acinetobacter baumannii
  • Anti-Bacterial Agents
  • Bacterial Outer Membrane Proteins
  • Bacterial Proteins
  • Escherichia coli Proteins
  • Lipoproteins
  • Membrane Transport Proteins
  • Multidrug Resistance-Associated Proteins
  • Recombinant Proteins
  • beta-Lactams
  • tolC protein, E coli
  • Novobiocin
  • Erythromycin
  • beta-Lactamases
  • Ethidium
  • Tetracycline