Functional membrane microdomains and the hydroxamate siderophore transporter ATPase FhuC govern Isd-dependent heme acquisition in Staphylococcus aureus
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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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Cites
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764 · see citing works
Siderophore-Based Iron Acquisition and Pathogen Control
Miethke, M., & Marahiel, M. A. (2007) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00012-07 · Cited by 1,774 · see citing works
Iron in infection and immunity
Cassat, J. E., & Skaar, E. P. (2013) · Cell Host & Microbe · doi:10.1016/j.chom.2013.04.010 · Cited by 1,214 · see citing works
Nutritional immunity: the battle for nutrient metals at the host–pathogen interface
Murdoch, C. C., & Skaar, E. P. (2022) · Nature Reviews Microbiology · doi:10.1038/s41579-022-00745-6 · Cited by 701 · see citing works
Passage of Heme-Iron Across the Envelope of <i>Staphylococcus aureus</i>
Mazmanian, S. K., Skaar, E. P., Gaspar, A. H., Humayun, M., Gornicki, P., Jelenska, J., Joachmiak, A., Missiakas, D. M., & Schneewind, O. (2003) · Science · doi:10.1126/science.1081147 · Cited by 593 · see citing works
Iron-Source Preference of <i>Staphylococcus aureus</i> Infections
Skaar, E. P., Humayun, M., Bae, T., DeBord, K. L., & Schneewind, O. (2004) · Science · doi:10.1126/science.1099930 · Cited by 440 · see citing works
Mazmanian, S. K., Ton-That, H., Su, K., & Schneewind, O. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.032523999 · Cited by 372 · see citing works
Iron acquisition strategies of bacterial pathogens
Sheldon, J. R., Laakso, H. A., & Heinrichs, D. E. (2016) · Microbiology Spectrum · doi:10.1128/microbiolspec.vmbf-0010-2015 · Cited by 219 · see citing works
Beasley, F. C., Vinés, E. D., Grigg, J. C., Zheng, Q., Liu, S., Lajoie, G. A., Murphy, M. E. P., & Heinrichs, D. E. (2009) · Molecular Microbiology · doi:10.1111/j.1365-2958.2009.06698.x · Cited by 163 · see citing works
Beasley, F. C., Marolda, C. L., Cheung, J., Buac, S., & Heinrichs, D. E. (2011) · Infection and Immunity · doi:10.1128/iai.00117-11 · Cited by 151 · see citing works
<i>Bacillus anthracis</i>IsdG, a Heme-Degrading Monooxygenase
Skaar, E. P., Gaspar, A. H., & Schneewind, O. (2006) · Journal of Bacteriology · doi:10.1128/jb.188.3.1071-1080.2006 · Cited by 123 · see citing works
Staphylococcus aureus Targets the Duffy Antigen Receptor for Chemokines (DARC) to Lyse Erythrocytes
Spaan, A. N., Reyes-Robles, T., Badiou, C., Cochet, S., Boguslawski, K. M., Yoong, P., Day, C. J., de Haas, C. J. C., van Kessel, K. P. M., Vandenesch, F., et al. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.08.001 · Cited by 114 · see citing works
Cotton, J. L., Tao, J., & Balibar, C. J. (2009) · Biochemistry · doi:10.1021/bi801844c · Cited by 95 · see citing works
Gat, O., Zaide, G., Inbar, I., Grosfeld, H., Chitlaru, T., Levy, H., & Shafferman, A. (2008) · Molecular Microbiology · doi:10.1111/j.1365-2958.2008.06460.x · Cited by 68 · see citing works
Iron-Regulated Surface Determinant (Isd) Proteins of Staphylococcus lugdunensis
Zapotoczna, M., Heilbronner, S., Speziale, P., & Foster, T. J. (2012) · Journal of Bacteriology · doi:10.1128/jb.01195-12 · Cited by 56 · see citing works
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- Authors
- Adolf, L. A., Müller-Jochim, A., Kricks, L., Puls, J.-S., Lopez, D., Grein, F., & Heilbronner, S.
- Affiliations
- University of Tübingen (DE)
- Consejo Superior de Investigaciones Científicas (ES)
- University of Bonn (DE)
- National Centre for Biotechnology, Spanish National Research Council (CNB-CSIC)
- German Center for Infection Research (DE)
- Corresponding author
- Heilbronner, Simon
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2023-04-12
- Volume
- 12
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC10147376
- OpenAlex
- W4365135245
- Cited by
- 18
- References
- 15
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 4 · 2023: 2
- FWCI
- 2.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- German Center of Infection Research (TTU 08.708_00)
- Deutsche Forschungsgemeinschaft (EXC 2124 - 390838134, 398967434 -TRR261)
- Fortuene Program University Hospital Tuebingen (2507-0-0)
- Spanish Ministry of Science (PID2020-115699GB-100)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Keywords
- Staphylococcus aureus, heme acquisition, iron acquisition, siderophore transport, lipid rafts, bacterial cell envelope
- MeSH terms
- Adenosine Triphosphatases, Bacterial Proteins, Heme, Iron, Staphylococcus aureus, Siderophores, Membrane Transport Proteins
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