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

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) sys...

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Autores principales: Adolf, Lea Antje, Müller-Jochim, Angelika, Kricks, Lara, Puls, Jan-Samuel, Lopez, Daniel, Grein, Fabian, Heilbronner, Simon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10147376/
https://www.ncbi.nlm.nih.gov/pubmed/37042640
http://dx.doi.org/10.7554/eLife.85304
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author Adolf, Lea Antje
Müller-Jochim, Angelika
Kricks, Lara
Puls, Jan-Samuel
Lopez, Daniel
Grein, Fabian
Heilbronner, Simon
author_facet Adolf, Lea Antje
Müller-Jochim, Angelika
Kricks, Lara
Puls, Jan-Samuel
Lopez, Daniel
Grein, Fabian
Heilbronner, Simon
author_sort Adolf, Lea Antje
collection PubMed
description 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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spelling pubmed-101473762023-04-29 Functional membrane microdomains and the hydroxamate siderophore transporter ATPase FhuC govern Isd-dependent heme acquisition in Staphylococcus aureus Adolf, Lea Antje Müller-Jochim, Angelika Kricks, Lara Puls, Jan-Samuel Lopez, Daniel Grein, Fabian Heilbronner, Simon eLife Microbiology and Infectious Disease 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. eLife Sciences Publications, Ltd 2023-04-12 /pmc/articles/PMC10147376/ /pubmed/37042640 http://dx.doi.org/10.7554/eLife.85304 Text en © 2023, Adolf et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Microbiology and Infectious Disease
Adolf, Lea Antje
Müller-Jochim, Angelika
Kricks, Lara
Puls, Jan-Samuel
Lopez, Daniel
Grein, Fabian
Heilbronner, Simon
Functional membrane microdomains and the hydroxamate siderophore transporter ATPase FhuC govern Isd-dependent heme acquisition in Staphylococcus aureus
title Functional membrane microdomains and the hydroxamate siderophore transporter ATPase FhuC govern Isd-dependent heme acquisition in Staphylococcus aureus
title_full Functional membrane microdomains and the hydroxamate siderophore transporter ATPase FhuC govern Isd-dependent heme acquisition in Staphylococcus aureus
title_fullStr Functional membrane microdomains and the hydroxamate siderophore transporter ATPase FhuC govern Isd-dependent heme acquisition in Staphylococcus aureus
title_full_unstemmed Functional membrane microdomains and the hydroxamate siderophore transporter ATPase FhuC govern Isd-dependent heme acquisition in Staphylococcus aureus
title_short Functional membrane microdomains and the hydroxamate siderophore transporter ATPase FhuC govern Isd-dependent heme acquisition in Staphylococcus aureus
title_sort functional membrane microdomains and the hydroxamate siderophore transporter atpase fhuc govern isd-dependent heme acquisition in staphylococcus aureus
topic Microbiology and Infectious Disease
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10147376/
https://www.ncbi.nlm.nih.gov/pubmed/37042640
http://dx.doi.org/10.7554/eLife.85304
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