Functional membrane microdomains and the hydroxamate siderophore transporter ATPase FhuC govern Isd-dependent heme acquisition in Staphylococcus aureus

  1. Lea Antje Adolf
  2. Angelika Müller-Jochim
  3. Lara Kricks
  4. Jan-Samuel Puls
  5. Daniel Lopez
  6. Fabian Grein
  7. Simon Heilbronner  Is a corresponding author
  1. University of Tübingen, Germany
  2. Spanish National Research Council, Spain
  3. University of Bonn, Germany

Abstract

Sufficient access to transition metals such as iron is essential for bacterial proliferation and their active limitation within host tissues effectively restricts infection. To overcome iron limitation, the invasive pathogen Staphylococcus aureus uses the iron-regulated surface determinant (Isd) system to acquire hemoglobin-derived heme. While heme transport over the cell wall is well understood, its transport over the membrane is hardly investigated. In this study, we show the heme-specific permease IsdF to be energized by the general ATPase FhuC. Additionally, we show that IsdF needs appropriate location within the membrane for functionality. The membrane of S. aureus possesses special compartments (functional membrane microdomains - FMMs) to organize membrane complexes. We show IsdF to be associated with FMMs, to directly interact with the FMM scaffolding protein flotillin A (FloA) and to co-localize with the latter on intact bacterial cells. Additionally, Isd-dependent bacterial growth required FMMs and FloA. Our study shows that Isd-dependent heme acquisition requires a highly structured cell envelope to allow coordinated transport over the cell wall and membrane and it gives the first example of a bacterial nutrient acquisition system that depends on FMMs.

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Article and author information

Author details

  1. Lea Antje Adolf

    Department of Infection Biology, University of Tübingen, Tübingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Angelika Müller-Jochim

    Department of Infection Biology, University of Tübingen, Tübingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Lara Kricks

    National Centre for Biotechnology, Spanish National Research Council, Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  4. Jan-Samuel Puls

    Institute for Pharmaceutical Microbiology, University of Bonn, Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8130-7375
  5. Daniel Lopez

    National Centre for Biotechnology, Spanish National Research Council, Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8627-3813
  6. Fabian Grein

    Institute for Pharmaceutical Microbiology, University of Bonn, Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Simon Heilbronner

    Department of Infection Biology, University of Tübingen, Tübingen, Germany
    For correspondence
    simon.heilbronner@uni-tuebingen.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6774-2311

Funding

German Center of Infection Research (TTU 08.708_00)

  • Simon Heilbronner

Deutsche Forschungsgemeinschaft (EXC 2124 - 390838134)

  • Simon Heilbronner

Fortuene Program University Hospital Tuebingen (2507-0-0)

  • Simon Heilbronner

Spanish Ministry of Science (PID2020-115699GB-100)

  • Daniel Lopez

Deutsche Forschungsgemeinschaft (398967434 -TRR261)

  • Simon Heilbronner

Deutsche Forschungsgemeinschaft (398967434 -TRR261)

  • Fabian Grein

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

Copyright

© 2023, Adolf 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. Lea Antje Adolf
  2. Angelika Müller-Jochim
  3. Lara Kricks
  4. Jan-Samuel Puls
  5. Daniel Lopez
  6. Fabian Grein
  7. Simon Heilbronner
(2023)
Functional membrane microdomains and the hydroxamate siderophore transporter ATPase FhuC govern Isd-dependent heme acquisition in Staphylococcus aureus
eLife 12:e85304.
https://doi.org/10.7554/eLife.85304

Share this article

https://doi.org/10.7554/eLife.85304

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