Preacinetobactin not acinetobactin is essential for iron uptake by the BauA transporter of the pathogen Acinetobacter baumannii

  1. Lucile Moynie
  2. Ilaria Serra
  3. Mariano A Scorciapino
  4. Emilia Oueis
  5. Malcolm GP Page
  6. Matteo Ceccarelli
  7. James H Naismith  Is a corresponding author
  1. Wellcome Trust Centre of Human Genomics, United Kingdom
  2. University of Cagliari, Italy
  3. The University of St Andrews, United Kingdom
  4. Jacobs University, Germany

Abstract

New strategies are urgently required to develop antibiotics. The siderophore uptake system has attracted considerable attention but rational design of siderophore antibiotic conjugates requires knowledge of recognition by the cognate outer membrane transporter. Acinetobacter baumannii is a serious pathogen, which utilizes (pre)acinetobactin to scavenge iron from the host. We report the structure of the (pre)acinetobactin transporter BauA bound to the siderophore, identifying the structural determinants of recognition. Detailed biophysical analysis confirms that BauA recognises preacinetobactin. We show that acinetobactin is not recognised by the protein thus preacinetobactin is essential for iron uptake. The structure shows and NMR confirms that under physiological conditions a molecule of acinetobactin will bind to two free coordination sites on the iron preacinetobactin complex. The ability to recognise a heterotrimeric iron preacinetobactin acinetobactin complex may rationalize contradictory reports in the literature. These results open new avenues for the design of novel antibiotic conjugates (trojan horse) antibiotics.

Data availability

Diffraction data have been deposited in PDB under the accession codes 6H7F, 6H7V, 6HCP.

The following data sets were generated

Article and author information

Author details

  1. Lucile Moynie

    Division of Structural Biology, Wellcome Trust Centre of Human Genomics, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Ilaria Serra

    Department of Physics, University of Cagliari, Cagliari, Italy
    Competing interests
    The authors declare that no competing interests exist.
  3. Mariano A Scorciapino

    Department of Physics, University of Cagliari, Cagliari, Italy
    Competing interests
    The authors declare that no competing interests exist.
  4. Emilia Oueis

    The University of St Andrews, St Andrews, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0228-6394
  5. Malcolm GP Page

    Department of Life Sciences and Chemistry, Jacobs University, Bremen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Matteo Ceccarelli

    Department of Physics, University of Cagliari, Cagliari, Italy
    Competing interests
    The authors declare that no competing interests exist.
  7. James H Naismith

    Division of Structural Biology, Wellcome Trust Centre of Human Genomics, Oxford, United Kingdom
    For correspondence
    naismith@strubi.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6744-5061

Funding

European Union (115525)

  • Lucile Moynie
  • Ilaria Serra
  • Mariano A Scorciapino
  • Malcolm GP Page
  • Matteo Ceccarelli
  • James H Naismith

Wellcome (100209/Z/12/Z)

  • Lucile Moynie
  • James H Naismith

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

Reviewing Editor

  1. Wilfred A van der Donk, University of Illinois at Urbana-Champaign, United States

Publication history

  1. Received: September 24, 2018
  2. Accepted: December 2, 2018
  3. Accepted Manuscript published: December 18, 2018 (version 1)
  4. Version of Record published: December 19, 2018 (version 2)

Copyright

© 2018, Moynie 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. Lucile Moynie
  2. Ilaria Serra
  3. Mariano A Scorciapino
  4. Emilia Oueis
  5. Malcolm GP Page
  6. Matteo Ceccarelli
  7. James H Naismith
(2018)
Preacinetobactin not acinetobactin is essential for iron uptake by the BauA transporter of the pathogen Acinetobacter baumannii
eLife 7:e42270.
https://doi.org/10.7554/eLife.42270

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