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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American Society for Microbiology
2019
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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) |
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adhesion Staphylococcus aureus atomic force microscopy mechanical force von Willebrand factor Microbiology QR1-502 |
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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 |
work_keys_str_mv |
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