Abstract
Colonisation of humans by Staphylococcus aureus is a major risk factor for infection, yet the bacterial and host factors involved are not fully understood. The first step during skin colonisation is adhesion of the bacteria to corneocytes in the stratum corneum where the cornified envelope protein loricrin is the main ligand for S. aureus. Here we report a novel loricrin-binding protein of S. aureus, the cell wall-anchored fibronectin binding protein B (FnBPB). Single-molecule force spectroscopy revealed both weak and ultra-strong (2 nN) binding of FnBPB to loricrin and that mechanical stress enhanced the strength of these bonds. Treatment with a peptide derived from fibrinogen decreased the frequency of strong interactions, suggesting that both ligands bind to overlapping sites within FnBPB. Finally, we show that FnBPB promotes adhesion to human corneocytes by binding strongly to loricrin, highlighting the relevance of this interaction to skin colonisation.
Original language | English |
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Article number | 2517 |
Number of pages | 11 |
Journal | Nature Communications |
Volume | 13 |
Issue number | 1 |
Early online date | 6 May 2022 |
DOIs | |
Publication status | Published - Dec 2022 |
Bibliographical note
Funding Information:T.M.d.C. was supported by the Irish Research Council under grant number GOIPD/2018/709. Work at Trinity College Dublin was also supported by a British Skin Foundation Research Project Grant 7013 s to J.A.G. Work at the UCLouvain was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement n°693630) and the National Fund for Scientific Research (FNRS). We thank Martin Sutton, Mary Turley, Sara Henderson and Tim Foster for helpful discussion, and Deirdre Muldowney for technical assistance.
Publisher Copyright:
© 2022, The Author(s).
Keywords
- Adhesins, Bacterial/chemistry
- Bacterial Adhesion
- Fibronectins/metabolism
- Humans
- Membrane Proteins
- Protein Binding
- Staphylococcal Infections/microbiology
- Staphylococcus aureus/metabolism
ASJC Scopus subject areas
- Physics and Astronomy(all)
- Chemistry(all)
- Biochemistry, Genetics and Molecular Biology(all)