Evans, Dominique, Khamas, Amanda, Payne-Dwyer, Alex orcid.org/0000-0001-8802-352X et al. (6 more authors) (2024) Cooperation between Coagulase and von Willebrand factor binding protein in Staphylococcus aureus fibrin pseudocapsule formation. Biofilm. 100233. ISSN 2590-2075
Abstract
The major human pathogen Staphylococcus aureus forms biofilms comprising of a fibrin network that increases attachment to surfaces and shields bacteria from the immune system. It secretes two coagulases, Coagulase (Coa) and von Willebrand factor binding protein (vWbp), which hijack the host coagulation cascade and trigger the formation of this fibrin clot. However, it is unclear how Coa and vWbp contribute differently to the localisation and dynamics of clot assembly in growing biofilms. Here, we address this question using high-precision time-resolved confocal microscopy of fluorescent fibrin to establish the spatiotemporal dynamics of fibrin clot formation in functional biofilms. We also use fluorescent fusion proteins to visualise the locations of Coa and vWbp in biofilms using both confocal laser scanning and high resolution highly inclined and laminated optical sheet microscopy. We visualise and quantify the spatiotemporal dynamics of fibrin production during initiation of biofilms in plasma amended with fluorescently labelled fibrinogen. We find that human serum stimulates coagulase production, and that Coa and vWbp loosely associate to the bacterial cell surface. Coa localises to cell surfaces to produce a surface-attached fibrin pseudocapsule but can diffuse from cells to produce matrix-associated fibrin. vWbp produces matrix-associated fibrin in the absence of Coa, and furthermore accelerates pseudocapsule production when Coa is present. Finally, we observe that fibrin production varies across the biofilm. A sub-population of non-dividing cells does not produce any pseudocapsule but remains within the protective extended fibrin network, which could be important for the persistence of S. aureus biofilm infections as antibiotics are more effective against actively growing cells.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 The Authors. |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) The University of York > Faculty of Sciences (York) > Physics (York) |
Depositing User: | Pure (York) |
Date Deposited: | 04 Nov 2024 14:20 |
Last Modified: | 23 Dec 2024 00:17 |
Published Version: | https://doi.org/10.1016/j.bioflm.2024.100233 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1016/j.bioflm.2024.100233 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:219225 |
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Filename: Manuscript_on_Coa_vWbp_and_SI_AAM.pdf
Description: Manuscript on Coa vWbp and SI, AAM
Licence: CC-BY 2.5