Functional membrane microdomains and the hydroxamate siderophore transporter ATPase FhuC govern Isd-dependent heme acquisition in Staphylococcus aureus
Lea Antje Adolf,
Angelika Müller-Jochim,
Lara Kricks,
Jan-Samuel Puls,
Daniel Lopez,
Fabian Grein,
Simon Heilbronner
Affiliations
Lea Antje Adolf
Department of Infection Biology, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany; Cluster of Excellence EXC 2124 Controlling Microbes to Fight Infections, Tübingen, Germany; Interfaculty Institute of Microbiology and Infection Medicine, Institute for Medical Microbiology and Hygiene, UKT Tübingen, Tübingen, Germany
Angelika Müller-Jochim
Department of Infection Biology, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany; Cluster of Excellence EXC 2124 Controlling Microbes to Fight Infections, Tübingen, Germany; Interfaculty Institute of Microbiology and Infection Medicine, Institute for Medical Microbiology and Hygiene, UKT Tübingen, Tübingen, Germany
Lara Kricks
National Centre for Biotechnology, Spanish National Research Council (CNB-CSIC), Madrid, Spain; Research Centre for Infectious Diseases (ZINF), University of Würzburg, Würzburg, Germany; Institute for Molecular Infection Biology (IMIB), University of Würzburg, Würzburg, Germany
National Centre for Biotechnology, Spanish National Research Council (CNB-CSIC), Madrid, Spain; Research Centre for Infectious Diseases (ZINF), University of Würzburg, Würzburg, Germany; Institute for Molecular Infection Biology (IMIB), University of Würzburg, Würzburg, Germany
Fabian Grein
Institute for Pharmaceutical Microbiology, University Hospital Bonn, University of Bonn, Bonn, Germany; German Center for Infection Research (DZIF), partner site Bonn-Cologne, Bonn, Germany
Department of Infection Biology, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany; Cluster of Excellence EXC 2124 Controlling Microbes to Fight Infections, Tübingen, Germany; Interfaculty Institute of Microbiology and Infection Medicine, Institute for Medical Microbiology and Hygiene, UKT Tübingen, Tübingen, Germany; German Center for Infection Research (DZIF), Tübingen, Germany; Faculty of Biology: Microbiology, Ludwig-Maximilians-Universität München, München, Germany
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.
