Fibrinogen Activates the Capture of Human Plasminogen by Staphylococcal Fibronectin-Binding Proteins

ABSTRACT Invasive bacterial pathogens can capture host plasminogen (Plg) and allow it to form plasmin. This process is of medical importance as surface-bound plasmin promotes bacterial spread by cleaving tissue components and favors immune evasion by degrading opsonins. In Staphylococcus aureus, Plg...

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Autores principales:	Philippe Herman-Bausier, Giampiero Pietrocola, Timothy J. Foster, Pietro Speziale, Yves F. Dufrêne
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	cell wall ligand binding Staphylococcus aureus surface proteins Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/f97385118d044026b1d24837cb117838
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spelling	oai:doaj.org-article:f97385118d044026b1d24837cb1178382021-11-15T15:51:50ZFibrinogen Activates the Capture of Human Plasminogen by Staphylococcal Fibronectin-Binding Proteins10.1128/mBio.01067-172150-7511https://doaj.org/article/f97385118d044026b1d24837cb1178382017-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01067-17https://doaj.org/toc/2150-7511ABSTRACT Invasive bacterial pathogens can capture host plasminogen (Plg) and allow it to form plasmin. This process is of medical importance as surface-bound plasmin promotes bacterial spread by cleaving tissue components and favors immune evasion by degrading opsonins. In Staphylococcus aureus, Plg binding is in part mediated by cell surface fibronectin-binding proteins (FnBPs), but the underlying molecular mechanism is not known. Here, we use single-cell and single-molecule techniques to demonstrate that FnBPs capture Plg by a sophisticated activation mechanism involving fibrinogen (Fg), another ligand found in the blood. We show that while FnBPs bind to Plg through weak (∼200-pN) molecular bonds, direct interaction of the adhesins with Fg through the high-affinity dock, lock, and latch mechanism dramatically increases the strength of the FnBP-Plg bond (up to ∼2,000 pN). Our results point to a new model in which the binding of Fg triggers major conformational changes in the FnBP protein, resulting in the buried Plg-binding domains being projected and exposed away from the cell surface, thereby promoting strong interactions with Plg. This study demonstrated a previously unidentified role for a ligand-binding interaction by a staphylococcal cell surface protein, i.e., changing the protein orientation to activate a cryptic biological function. IMPORTANCE Staphylococcus aureus captures human plasminogen (Plg) via cell wall fibronectin-binding proteins (FnBPs), but the underlying molecular mechanism is not known. Here we show that the forces involved in the interaction between Plg and FnBPs on the S. aureus surface are weak. However, we discovered that binding of fibrinogen to FnBPs dramatically strengthens the FnBP-Plg bond, therefore revealing an unanticipated role for Fg in the capture of Plg by S. aureus. These experiments favor a model where Fg-induced conformational changes in FnBPs promote their interaction with Plg. This work uncovers a previously undescribed activation mechanism for a staphylococcal surface protein, whereby ligand-binding elicits a cryptic biological function.Philippe Herman-BausierGiampiero PietrocolaTimothy J. FosterPietro SpezialeYves F. DufrêneAmerican Society for Microbiologyarticlecell wallligand bindingStaphylococcus aureussurface proteinsMicrobiologyQR1-502ENmBio, Vol 8, Iss 5 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	cell wall ligand binding Staphylococcus aureus surface proteins Microbiology QR1-502
spellingShingle	cell wall ligand binding Staphylococcus aureus surface proteins Microbiology QR1-502 Philippe Herman-Bausier Giampiero Pietrocola Timothy J. Foster Pietro Speziale Yves F. Dufrêne Fibrinogen Activates the Capture of Human Plasminogen by Staphylococcal Fibronectin-Binding Proteins
description	ABSTRACT Invasive bacterial pathogens can capture host plasminogen (Plg) and allow it to form plasmin. This process is of medical importance as surface-bound plasmin promotes bacterial spread by cleaving tissue components and favors immune evasion by degrading opsonins. In Staphylococcus aureus, Plg binding is in part mediated by cell surface fibronectin-binding proteins (FnBPs), but the underlying molecular mechanism is not known. Here, we use single-cell and single-molecule techniques to demonstrate that FnBPs capture Plg by a sophisticated activation mechanism involving fibrinogen (Fg), another ligand found in the blood. We show that while FnBPs bind to Plg through weak (∼200-pN) molecular bonds, direct interaction of the adhesins with Fg through the high-affinity dock, lock, and latch mechanism dramatically increases the strength of the FnBP-Plg bond (up to ∼2,000 pN). Our results point to a new model in which the binding of Fg triggers major conformational changes in the FnBP protein, resulting in the buried Plg-binding domains being projected and exposed away from the cell surface, thereby promoting strong interactions with Plg. This study demonstrated a previously unidentified role for a ligand-binding interaction by a staphylococcal cell surface protein, i.e., changing the protein orientation to activate a cryptic biological function. IMPORTANCE Staphylococcus aureus captures human plasminogen (Plg) via cell wall fibronectin-binding proteins (FnBPs), but the underlying molecular mechanism is not known. Here we show that the forces involved in the interaction between Plg and FnBPs on the S. aureus surface are weak. However, we discovered that binding of fibrinogen to FnBPs dramatically strengthens the FnBP-Plg bond, therefore revealing an unanticipated role for Fg in the capture of Plg by S. aureus. These experiments favor a model where Fg-induced conformational changes in FnBPs promote their interaction with Plg. This work uncovers a previously undescribed activation mechanism for a staphylococcal surface protein, whereby ligand-binding elicits a cryptic biological function.
format	article
author	Philippe Herman-Bausier Giampiero Pietrocola Timothy J. Foster Pietro Speziale Yves F. Dufrêne
author_facet	Philippe Herman-Bausier Giampiero Pietrocola Timothy J. Foster Pietro Speziale Yves F. Dufrêne
author_sort	Philippe Herman-Bausier
title	Fibrinogen Activates the Capture of Human Plasminogen by Staphylococcal Fibronectin-Binding Proteins
title_short	Fibrinogen Activates the Capture of Human Plasminogen by Staphylococcal Fibronectin-Binding Proteins
title_full	Fibrinogen Activates the Capture of Human Plasminogen by Staphylococcal Fibronectin-Binding Proteins
title_fullStr	Fibrinogen Activates the Capture of Human Plasminogen by Staphylococcal Fibronectin-Binding Proteins
title_full_unstemmed	Fibrinogen Activates the Capture of Human Plasminogen by Staphylococcal Fibronectin-Binding Proteins
title_sort	fibrinogen activates the capture of human plasminogen by staphylococcal fibronectin-binding proteins
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/f97385118d044026b1d24837cb117838
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Fibrinogen Activates the Capture of Human Plasminogen by Staphylococcal Fibronectin-Binding Proteins

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