Staphylococcus aureus iron-regulated surface determinant B (IsdB) protein interacts with von Willebrand factor and promotes adherence to endothelial cells

Abstract Staphylococcus aureus is the cause of a spectrum of diseases in humans and animals. The molecular basis of this pathogenicity lies in the expression of a variety of virulence factors, including proteins that mediate adherence to the host plasma and extracellular matrix proteins. In this stu...

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Autores principales:	Mariangela J. Alfeo, Anna Pagotto, Giulia Barbieri, Timothy J. Foster, Karen Vanhoorelbeke, Vincenzo De Filippis, Pietro Speziale, Giampiero Pietrocola
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f7e8f93752b14d3a8ee37736626950c6
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spelling	oai:doaj.org-article:f7e8f93752b14d3a8ee37736626950c62021-11-28T12:21:14ZStaphylococcus aureus iron-regulated surface determinant B (IsdB) protein interacts with von Willebrand factor and promotes adherence to endothelial cells10.1038/s41598-021-02065-w2045-2322https://doaj.org/article/f7e8f93752b14d3a8ee37736626950c62021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02065-whttps://doaj.org/toc/2045-2322Abstract Staphylococcus aureus is the cause of a spectrum of diseases in humans and animals. The molecular basis of this pathogenicity lies in the expression of a variety of virulence factors, including proteins that mediate adherence to the host plasma and extracellular matrix proteins. In this study, we discovered that the iron-regulated surface determinant B (IsdB) protein, besides being involved in iron transport and vitronectin binding, interacts with von Willebrand Factor (vWF). IsdB-expressing bacteria bound to both soluble and immobilized vWF. The binding of recombinant IsdB to vWF was blocked by heparin and reduced at high ionic strength. Furthermore, treatment with ristocetin, an allosteric agent that promotes the exposure of the A1 domain of vWF, potentiates the binding of IsdB to vWF. Both near-iron transporter motifs NEAT1 and NEAT2 of IsdB individually bound recombinant A1 domain with KD values in the micromolar range. The binding of IsdB and adhesion of S. aureus expressing IsdB to monolayers of activated endothelial cells was significantly inhibited by a monoclonal antibody against the A1 domain and by IsdB reactive IgG from patients with staphylococcal endocarditis. This suggests the importance of IsdB in adherence of S. aureus to the endothelium colonization and as potential therapeutic target.Mariangela J. AlfeoAnna PagottoGiulia BarbieriTimothy J. FosterKaren VanhoorelbekeVincenzo De FilippisPietro SpezialeGiampiero PietrocolaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mariangela J. Alfeo Anna Pagotto Giulia Barbieri Timothy J. Foster Karen Vanhoorelbeke Vincenzo De Filippis Pietro Speziale Giampiero Pietrocola Staphylococcus aureus iron-regulated surface determinant B (IsdB) protein interacts with von Willebrand factor and promotes adherence to endothelial cells
description	Abstract Staphylococcus aureus is the cause of a spectrum of diseases in humans and animals. The molecular basis of this pathogenicity lies in the expression of a variety of virulence factors, including proteins that mediate adherence to the host plasma and extracellular matrix proteins. In this study, we discovered that the iron-regulated surface determinant B (IsdB) protein, besides being involved in iron transport and vitronectin binding, interacts with von Willebrand Factor (vWF). IsdB-expressing bacteria bound to both soluble and immobilized vWF. The binding of recombinant IsdB to vWF was blocked by heparin and reduced at high ionic strength. Furthermore, treatment with ristocetin, an allosteric agent that promotes the exposure of the A1 domain of vWF, potentiates the binding of IsdB to vWF. Both near-iron transporter motifs NEAT1 and NEAT2 of IsdB individually bound recombinant A1 domain with KD values in the micromolar range. The binding of IsdB and adhesion of S. aureus expressing IsdB to monolayers of activated endothelial cells was significantly inhibited by a monoclonal antibody against the A1 domain and by IsdB reactive IgG from patients with staphylococcal endocarditis. This suggests the importance of IsdB in adherence of S. aureus to the endothelium colonization and as potential therapeutic target.
format	article
author	Mariangela J. Alfeo Anna Pagotto Giulia Barbieri Timothy J. Foster Karen Vanhoorelbeke Vincenzo De Filippis Pietro Speziale Giampiero Pietrocola
author_facet	Mariangela J. Alfeo Anna Pagotto Giulia Barbieri Timothy J. Foster Karen Vanhoorelbeke Vincenzo De Filippis Pietro Speziale Giampiero Pietrocola
author_sort	Mariangela J. Alfeo
title	Staphylococcus aureus iron-regulated surface determinant B (IsdB) protein interacts with von Willebrand factor and promotes adherence to endothelial cells
title_short	Staphylococcus aureus iron-regulated surface determinant B (IsdB) protein interacts with von Willebrand factor and promotes adherence to endothelial cells
title_full	Staphylococcus aureus iron-regulated surface determinant B (IsdB) protein interacts with von Willebrand factor and promotes adherence to endothelial cells
title_fullStr	Staphylococcus aureus iron-regulated surface determinant B (IsdB) protein interacts with von Willebrand factor and promotes adherence to endothelial cells
title_full_unstemmed	Staphylococcus aureus iron-regulated surface determinant B (IsdB) protein interacts with von Willebrand factor and promotes adherence to endothelial cells
title_sort	staphylococcus aureus iron-regulated surface determinant b (isdb) protein interacts with von willebrand factor and promotes adherence to endothelial cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f7e8f93752b14d3a8ee37736626950c6
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Staphylococcus aureus iron-regulated surface determinant B (IsdB) protein interacts with von Willebrand factor and promotes adherence to endothelial cells

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