Accessible Requires Authentication Published by De Gruyter June 9, 2015

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

Reinke Tobias Müller and Klaas Martinus Pos
From the journal Biological Chemistry

Abstract

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.


Corresponding author: Klaas Martinus Pos, Institute of Biochemistry, Goethe University Frankfurt, D-60438 Frankfurt/Main, Germany, e-mail:

Acknowledgments

Many of the ideas described in this review arose during the workshop ‘Toward an integrated understanding of drug resistance’ in Santa Fe, NM, USA on 18–20 February 2015. I would like to thank all the colleagues present at that occasion for their open discussion spirit. Work in the Pos lab is supported by the German Research Foundation (SFB 807, Transport and Communication across Biological Membranes and FOR2251, Adaptation and persistence of the emerging pathogen Acinetobacter baumannii), the DFG-EXC115 (Cluster of Excellence Macromolecular Complexes at the Goethe University Frankfurt), Innovative Medicines Initiative Joint Undertaking Project Translocation (IMI-Translocation), EU Marie Curie Actions ITN, Human Frontiers Science Program (HFSP) and the German-Israeli Foundation (GIF).

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Received: 2015-3-31
Accepted: 2015-6-3
Published Online: 2015-6-9
Published in Print: 2015-9-1

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