Abstract

Infections arising from multidrug-resistant pathogenic bacteria are spreading rapidly throughout the world and threaten to become untreatable. The origins of resistance are numerous and complex, but one underlying factor is the capacity of bacteria to rapidly export drugs through the intrinsic activity of efflux pumps. In this Review, we describe recent advances that have increased our understanding of the structures and molecular mechanisms of multidrug efflux pumps in bacteria. Clinical and laboratory data indicate that efflux pumps function not only in the drug extrusion process but also in virulence and the adaptive responses that contribute to antimicrobial resistance during infection. The emerging picture of the structure, function and regulation of efflux pumps suggests opportunities for countering their activities.

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Change history

  • 18 July 2018

    In the version of this Review originally published, the author contributions of co-author Arthur Neuberger were incorrectly listed. The author contributions should have appeared as ‘D.D., X.W.-K., A.N., H.W.v.V., K.M.P., L.J.V.P. and B.F.L. researched data for the article, made substantial contributions to discussions of the content, wrote the article, and reviewed and edited the manuscript before submission’. This has now been corrected in all versions of the Review. The authors apologize to readers for this error.

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Acknowledgements

The authors thank S. Murakami, B. Görke, J. Blaza, M. Welch, A. Vargiu, P. Ruggerone, L. Schmitt, and M. Osman for helpful discussions and the reviewers for helpful comments. B.F.L. and D.D. are supported by the Wellcome Trust and the European Research Council (742210). K.M.P. is supported by the German Research Foundation (DFG-SFB 807, ‘Transport and Communication across Biological Membranes’, and DFG-FOR2251, ‘Adaptation and Persistence of the Emerging Pathogen Acinetobacter baumannii), the DFG-EXC115 (Cluster of Excellence Frankfurt—Macromolecular Complexes), the Innovative Medicines Joint Undertaking (IMI-Translocation) under grant agreement no. 115525 and the National Institute of Allergy and Infectious Diseases (grant R44 AI100332). H.W.v.V., K.M.P. and B.F.L. are supported by a grant from the Human Frontier Science Program (RGP0034/2013). H.W.v.V. is also supported by the Biotechnology and Biological Sciences Research Council (grant BB/R00224X/1). A.N. is a recipient of a Herchel Smith Scholarship. X.W.-K. is supported by Consejo Nacional de Ciencia y Tecnología (CONACyT), Mexico. L.J.V.P. is supported by the Biotechnology and Biological Sciences Research Council (grant BB/N014200/1) and the Medical Research Council (MR/022596/1).

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Nature Reviews Microbiology thanks K. Beis, H. Schweizer and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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Affiliations

  1. Department of Biochemistry, University of Cambridge, Cambridge, UK

    • Dijun Du
    • , Arthur Neuberger
    •  & Ben F. Luisi
  2. Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK

    • Xuan Wang-Kan
    •  & Laura J. V. Piddock
  3. Department of Pharmacology, University of Cambridge, Cambridge, UK

    • Arthur Neuberger
    •  & Hendrik W. van Veen
  4. Institute of Biochemistry, Goethe Universität Frankfurt, Frankfurt, Germany

    • Klaas M. Pos

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D.D., X.W.-K., A.N., H.W.v.V., K.M.P., L.J.V.P. and B.F.L. researched data for the article, made substantial contributions to discussions of the content, wrote the article, and reviewed and edited the manuscript before submission.

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Correspondence to Ben F. Luisi.

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https://doi.org/10.1038/s41579-018-0048-6