The Acinetobacter baumannii Mla system and glycerophospholipid transport to the outer membrane

Abstract

The outer membrane (OM) of Gram-negative bacteria serves as a selective permeability barrier that allows entry of essential nutrients while excluding toxic compounds, including antibiotics. The OM is asymmetric and contains an outer leaflet of lipopolysaccharides (LPS) or lipooligosaccharides (LOS) and an inner leaflet of glycerophospholipids (GPL). We screened Acinetobacter baumannii transposon mutants and identified a number of mutants with OM defects, including an ABC transporter system homologous to the Mla system in E. coli. We further show that this opportunistic, antibiotic-resistant pathogen uses this multicomponent protein complex and ATP hydrolysis at the inner membrane to promote GPL export to the OM. The broad conservation of the Mla system in Gram-negative bacteria suggests the system may play a conserved role in OM biogenesis. The importance of the Mla system to Acinetobacter baumannii OM integrity and antibiotic sensitivity suggests that its components may serve as new antimicrobial therapeutic targets.

Data availability

The cryo-EM map has been deposited in the Electron Microscopy Data Bank with accession code EMD-8738 (8.7 Å map). The coordinates for the MlaBDEF model have been deposited to PDB, accession code 6IC4.

The following data sets were generated

Article and author information

Author details

  1. Cassandra Kamischke

    Department of Microbiology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Junping Fan

    Department of Microbiology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Julien Bergeron

    Department of Biochemistry, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Hemantha D Kulasekara

    Department of Microbiology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Zachary D Dalebroux

    Department of Microbiology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Anika Burrell

    Department of Biochemistry, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Justin M Kollman

    Department of Biochemistry, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Samuel I Miller

    Department of Microbiology, University of Washington, Seattle, United States
    For correspondence
    millersi@uw.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1638-2181

Funding

National Institute of Allergy and Infectious Diseases (U19AI107775)

  • Samuel I Miller

National Institutes of Health (R01GM118396)

  • Justin M Kollman

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Tâm Mignot, Aix Marseille University-CNRS UMR7283, France

Publication history

  1. Received: July 17, 2018
  2. Accepted: January 11, 2019
  3. Accepted Manuscript published: January 14, 2019 (version 1)
  4. Version of Record published: February 6, 2019 (version 2)

Copyright

© 2019, Kamischke et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Cassandra Kamischke
  2. Junping Fan
  3. Julien Bergeron
  4. Hemantha D Kulasekara
  5. Zachary D Dalebroux
  6. Anika Burrell
  7. Justin M Kollman
  8. Samuel I Miller
(2019)
The Acinetobacter baumannii Mla system and glycerophospholipid transport to the outer membrane
eLife 8:e40171.
https://doi.org/10.7554/eLife.40171
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