Functional membrane microdomains and the hydroxamate siderophore transporter ATPase FhuC govern Isd-dependent heme acquisition in Staphylococcus aureus
- University of Tübingen, Germany
- Spanish National Research Council, Spain
- 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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Author details
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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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
