Binding of <italic toggle="yes">Staphylococcus aureus</italic> Protein A to von Willebrand Factor Is Regulated by Mechanical Force

ABSTRACT Binding of Staphylococcus aureus to the large plasma glycoprotein von Willebrand factor (vWF) is controlled by hydrodynamic flow conditions. Currently, we know little about the molecular details of this shear-stress-dependent interaction. Using single-molecule atomic force microscopy, we de...

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Autores principales: Felipe Viela, Valeria Prystopiuk, Audrey Leprince, Jacques Mahillon, Pietro Speziale, Giampiero Pietrocola, Yves F. Dufrêne
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Publicado: American Society for Microbiology 2019
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spelling oai:doaj.org-article:cd5b06a9c04040ef92294f1b2489ab962021-11-15T15:55:25ZBinding of <italic toggle="yes">Staphylococcus aureus</italic> Protein A to von Willebrand Factor Is Regulated by Mechanical Force10.1128/mBio.00555-192150-7511https://doaj.org/article/cd5b06a9c04040ef92294f1b2489ab962019-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00555-19https://doaj.org/toc/2150-7511ABSTRACT Binding of Staphylococcus aureus to the large plasma glycoprotein von Willebrand factor (vWF) is controlled by hydrodynamic flow conditions. Currently, we know little about the molecular details of this shear-stress-dependent interaction. Using single-molecule atomic force microscopy, we demonstrate that vWF binds to the S. aureus surface protein A (SpA) via a previously undescribed force-sensitive mechanism. We identify an extremely strong SpA-vWF interaction, capable of withstanding forces of ∼2 nN, both in laboratory and in clinically relevant methicillin-resistant S. aureus (MRSA) strains. Strong bonds are activated by mechanical stress, consistent with flow experiments revealing that bacteria adhere in larger amounts to vWF surfaces when the shear rate is increased. We suggest that force-enhanced adhesion may involve conformational changes in vWF. Under force, elongation of vWF may lead to the exposure of a high-affinity cryptic SpA-binding site to which bacteria firmly attach. In addition, force-induced structural changes in the SpA domains may also promote strong, high-affinity binding. This force-regulated interaction might be of medical importance as it may play a role in bacterial adherence to platelets and to damaged blood vessels. IMPORTANCE Staphylococcus aureus protein A (SpA) binds to von Willebrand factor (vWF) under flow. While vWF binding to SpA plays a role in S. aureus adherence to platelets and endothelial cells under shear stress, the molecular basis of this stress-dependent interaction has not yet been elucidated. Here we show that the SpA-vWF interaction is regulated by a new force-dependent mechanism. The results suggest that mechanical extension of vWF may lead to the exposure of a high-affinity cryptic SpA-binding site, consistent with the shear force-controlled functions of vWF. Moreover, strong binding may be promoted by force-induced structural changes in the SpA domains. This study highlights the role of mechanoregulation in controlling the adhesion of S. aureus and shows promise for the design of small inhibitors capable of blocking colonization under high shear stress.Felipe VielaValeria PrystopiukAudrey LeprinceJacques MahillonPietro SpezialeGiampiero PietrocolaYves F. DufrêneAmerican Society for MicrobiologyarticleadhesionStaphylococcus aureusatomic force microscopymechanical forcevon Willebrand factorMicrobiologyQR1-502ENmBio, Vol 10, Iss 2 (2019)
institution DOAJ
collection DOAJ
language EN
topic adhesion
Staphylococcus aureus
atomic force microscopy
mechanical force
von Willebrand factor
Microbiology
QR1-502
spellingShingle adhesion
Staphylococcus aureus
atomic force microscopy
mechanical force
von Willebrand factor
Microbiology
QR1-502
Felipe Viela
Valeria Prystopiuk
Audrey Leprince
Jacques Mahillon
Pietro Speziale
Giampiero Pietrocola
Yves F. Dufrêne
Binding of <italic toggle="yes">Staphylococcus aureus</italic> Protein A to von Willebrand Factor Is Regulated by Mechanical Force
description ABSTRACT Binding of Staphylococcus aureus to the large plasma glycoprotein von Willebrand factor (vWF) is controlled by hydrodynamic flow conditions. Currently, we know little about the molecular details of this shear-stress-dependent interaction. Using single-molecule atomic force microscopy, we demonstrate that vWF binds to the S. aureus surface protein A (SpA) via a previously undescribed force-sensitive mechanism. We identify an extremely strong SpA-vWF interaction, capable of withstanding forces of ∼2 nN, both in laboratory and in clinically relevant methicillin-resistant S. aureus (MRSA) strains. Strong bonds are activated by mechanical stress, consistent with flow experiments revealing that bacteria adhere in larger amounts to vWF surfaces when the shear rate is increased. We suggest that force-enhanced adhesion may involve conformational changes in vWF. Under force, elongation of vWF may lead to the exposure of a high-affinity cryptic SpA-binding site to which bacteria firmly attach. In addition, force-induced structural changes in the SpA domains may also promote strong, high-affinity binding. This force-regulated interaction might be of medical importance as it may play a role in bacterial adherence to platelets and to damaged blood vessels. IMPORTANCE Staphylococcus aureus protein A (SpA) binds to von Willebrand factor (vWF) under flow. While vWF binding to SpA plays a role in S. aureus adherence to platelets and endothelial cells under shear stress, the molecular basis of this stress-dependent interaction has not yet been elucidated. Here we show that the SpA-vWF interaction is regulated by a new force-dependent mechanism. The results suggest that mechanical extension of vWF may lead to the exposure of a high-affinity cryptic SpA-binding site, consistent with the shear force-controlled functions of vWF. Moreover, strong binding may be promoted by force-induced structural changes in the SpA domains. This study highlights the role of mechanoregulation in controlling the adhesion of S. aureus and shows promise for the design of small inhibitors capable of blocking colonization under high shear stress.
format article
author Felipe Viela
Valeria Prystopiuk
Audrey Leprince
Jacques Mahillon
Pietro Speziale
Giampiero Pietrocola
Yves F. Dufrêne
author_facet Felipe Viela
Valeria Prystopiuk
Audrey Leprince
Jacques Mahillon
Pietro Speziale
Giampiero Pietrocola
Yves F. Dufrêne
author_sort Felipe Viela
title Binding of <italic toggle="yes">Staphylococcus aureus</italic> Protein A to von Willebrand Factor Is Regulated by Mechanical Force
title_short Binding of <italic toggle="yes">Staphylococcus aureus</italic> Protein A to von Willebrand Factor Is Regulated by Mechanical Force
title_full Binding of <italic toggle="yes">Staphylococcus aureus</italic> Protein A to von Willebrand Factor Is Regulated by Mechanical Force
title_fullStr Binding of <italic toggle="yes">Staphylococcus aureus</italic> Protein A to von Willebrand Factor Is Regulated by Mechanical Force
title_full_unstemmed Binding of <italic toggle="yes">Staphylococcus aureus</italic> Protein A to von Willebrand Factor Is Regulated by Mechanical Force
title_sort binding of <italic toggle="yes">staphylococcus aureus</italic> protein a to von willebrand factor is regulated by mechanical force
publisher American Society for Microbiology
publishDate 2019
url https://doaj.org/article/cd5b06a9c04040ef92294f1b2489ab96
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