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In situ structure and assembly of the multidrug efflux pump AcrAB-TolC

Author

Listed:
  • Xiaodong Shi

    (Baylor College of Medicine
    Xuzhou Medical University)

  • Muyuan Chen

    (Baylor College of Medicine)

  • Zhili Yu

    (Baylor College of Medicine)

  • James M. Bell

    (Baylor College of Medicine
    Baylor College of Medicine)

  • Hans Wang

    (Baylor College of Medicine)

  • Isaac Forrester

    (CryoEM Core at Baylor College of Medicine)

  • Heather Villarreal

    (CryoEM Core at Baylor College of Medicine)

  • Joanita Jakana

    (CryoEM Core at Baylor College of Medicine)

  • Dijun Du

    (University of Cambridge
    ShanghaiTech University)

  • Ben F. Luisi

    (University of Cambridge)

  • Steven J. Ludtke

    (Baylor College of Medicine)

  • Zhao Wang

    (Baylor College of Medicine
    Baylor College of Medicine)

Abstract

Multidrug efflux pumps actively expel a wide range of toxic substrates from the cell and play a major role in intrinsic and acquired drug resistance. In Gram-negative bacteria, these pumps form tripartite assemblies that span the cell envelope. However, the in situ structure and assembly mechanism of multidrug efflux pumps remain unknown. Here we report the in situ structure of the Escherichia coli AcrAB-TolC multidrug efflux pump obtained by electron cryo-tomography and subtomogram averaging. The fully assembled efflux pump is observed in a closed state under conditions of antibiotic challenge and in an open state in the presence of AcrB inhibitor. We also observe intermediate AcrAB complexes without TolC and discover that AcrA contacts the peptidoglycan layer of the periplasm. Our data point to a sequential assembly process in living bacteria, beginning with formation of the AcrAB subcomplex and suggest domains to target with efflux pump inhibitors.

Suggested Citation

  • Xiaodong Shi & Muyuan Chen & Zhili Yu & James M. Bell & Hans Wang & Isaac Forrester & Heather Villarreal & Joanita Jakana & Dijun Du & Ben F. Luisi & Steven J. Ludtke & Zhao Wang, 2019. "In situ structure and assembly of the multidrug efflux pump AcrAB-TolC," Nature Communications, Nature, vol. 10(1), pages 1-6, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10512-6
    DOI: 10.1038/s41467-019-10512-6
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    Cited by:

    1. Alina Ornik-Cha & Julia Wilhelm & Jessica Kobylka & Hanno Sjuts & Attilio V. Vargiu & Giuliano Malloci & Julian Reitz & Anja Seybert & Achilleas S. Frangakis & Klaas M. Pos, 2021. "Structural and functional analysis of the promiscuous AcrB and AdeB efflux pumps suggests different drug binding mechanisms," Nature Communications, Nature, vol. 12(1), pages 1-14, December.

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