4.3 Article Proceedings Paper

The assembly and disassembly of the AcrAB-TolC three-component multidrug efflux pump

Journal

BIOLOGICAL CHEMISTRY
Volume 396, Issue 9-10, Pages 1083-1089

Publisher

WALTER DE GRUYTER GMBH
DOI: 10.1515/hsz-2015-0150

Keywords

antibiotic resistance; proton-motive force; transport; tripartite efflux pumps

Funding

  1. German Research Foundation [SFB 807, FOR2251]
  2. DFG-EXC115 (Cluster of Excellence Macromolecular Complexes at the Goethe University Frankfurt)
  3. Innovative Medicines Initiative Joint Undertaking Project Translocation (IMI-Translocation)
  4. EU Marie Curie Actions ITN
  5. Human Frontiers Science Program (HFSP)
  6. German-Israeli Foundation (GIF)

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In Gram-negative bacteria, tripartite efflux pumps, like AcrAB-TolC from Escherichia coli, play a prominent role in the resistance against multiple antibiotics. Transport of the drugs across the outer membrane and its coupling to the electrochemical gradient is dependent on the presence of all three components. As the activity of the E. coli AcrAB-TolC efflux pump is dependent on both the concentration of substrates and the extent of the electrochemical gradient across the inner membrane, the -dynamics of tripartite pump assembly and disassembly might be crucial for effective net transport of drugs towards the outside of the cell.

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