The Expression of von Willebrand Factor-Binding Protein Determines Joint-Invading Capacity of <named-content content-type="genus-species">Staphylococcus aureus</named-content>, a Core Mechanism of Septic Arthritis

ABSTRACT Septic arthritis, one of the most dangerous joint diseases, is predominantly caused by Staphylococcus aureus. In contrast, coagulase-negative staphylococci are rarely found in septic arthritis. We hypothesize that coagulases released by S. aureus, including coagulase (Coa) and von Willebran...

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Autores principales:	Manli Na, Zhicheng Hu, Majd Mohammad, Mariana do Nascimento Stroparo, Abukar Ali, Ying Fei, Anders Jarneborn, Peter Verhamme, Olaf Schneewind, Dominique Missiakas, Tao Jin
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	von Willebrand factor-binding protein von Willebrand factor Staphylococcus aureus septic arthritis mouse Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/cd913e0415954e00a89e814833bb6a1a
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spelling	oai:doaj.org-article:cd913e0415954e00a89e814833bb6a1a2021-11-15T15:55:43ZThe Expression of von Willebrand Factor-Binding Protein Determines Joint-Invading Capacity of <named-content content-type="genus-species">Staphylococcus aureus</named-content>, a Core Mechanism of Septic Arthritis10.1128/mBio.02472-202150-7511https://doaj.org/article/cd913e0415954e00a89e814833bb6a1a2020-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02472-20https://doaj.org/toc/2150-7511ABSTRACT Septic arthritis, one of the most dangerous joint diseases, is predominantly caused by Staphylococcus aureus. In contrast, coagulase-negative staphylococci are rarely found in septic arthritis. We hypothesize that coagulases released by S. aureus, including coagulase (Coa) and von Willebrand factor-binding protein (vWbp), play potent roles in the induction of septic arthritis. Four isogenic S. aureus strains differing in expression of coagulases (wild-type [WT] Newman, Δcoa, Δvwb, and Δcoa Δvwb) were used to induce septic arthritis in both wild-type and von Willebrand factor (vWF)-deficient mice. Septic arthritis severity was greatly reduced when wild-type mice were infected with the Δcoa Δvwb and Δvwb variants compared to WT or Δcoa strains, suggesting that vWbp rather than Coa is a major virulence factor in S. aureus septic arthritis. vWF-deficient mice were more susceptible to bone damage in septic arthritis, especially when the Δvwb strain was used. Importantly, no difference in arthritis severity between the Δvwb and WT strains was observed in vWF-deficient mice. Collectively, we conclude that vWbp production by S. aureus enhances staphylococcal septic arthritis. IMPORTANCE Septic arthritis remains one of the most dangerous joint diseases with a rapidly progressive disease character. Despite advances in the use of antibiotics, permanent reductions in joint function due to joint deformation and deleterious contractures occur in up to 50% of patients with septic arthritis. So far, it is still largely unknown how S. aureus initiates and establishes joint infection. Here, we demonstrate that von Willebrand factor-binding protein expressed by S. aureus facilitates the initiation of septic arthritis. Such effect might be mediated through its interaction with a host factor (von Willebrand factor). Our finding contributes significantly to the full understanding of septic arthritis etiology and will pave the way for new therapeutic modalities for this devastating disease.Manli NaZhicheng HuMajd MohammadMariana do Nascimento StroparoAbukar AliYing FeiAnders JarnebornPeter VerhammeOlaf SchneewindDominique MissiakasTao JinAmerican Society for Microbiologyarticlevon Willebrand factor-binding proteinvon Willebrand factorStaphylococcus aureusseptic arthritismouseMicrobiologyQR1-502ENmBio, Vol 11, Iss 6 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	von Willebrand factor-binding protein von Willebrand factor Staphylococcus aureus septic arthritis mouse Microbiology QR1-502
spellingShingle	von Willebrand factor-binding protein von Willebrand factor Staphylococcus aureus septic arthritis mouse Microbiology QR1-502 Manli Na Zhicheng Hu Majd Mohammad Mariana do Nascimento Stroparo Abukar Ali Ying Fei Anders Jarneborn Peter Verhamme Olaf Schneewind Dominique Missiakas Tao Jin The Expression of von Willebrand Factor-Binding Protein Determines Joint-Invading Capacity of <named-content content-type="genus-species">Staphylococcus aureus</named-content>, a Core Mechanism of Septic Arthritis
description	ABSTRACT Septic arthritis, one of the most dangerous joint diseases, is predominantly caused by Staphylococcus aureus. In contrast, coagulase-negative staphylococci are rarely found in septic arthritis. We hypothesize that coagulases released by S. aureus, including coagulase (Coa) and von Willebrand factor-binding protein (vWbp), play potent roles in the induction of septic arthritis. Four isogenic S. aureus strains differing in expression of coagulases (wild-type [WT] Newman, Δcoa, Δvwb, and Δcoa Δvwb) were used to induce septic arthritis in both wild-type and von Willebrand factor (vWF)-deficient mice. Septic arthritis severity was greatly reduced when wild-type mice were infected with the Δcoa Δvwb and Δvwb variants compared to WT or Δcoa strains, suggesting that vWbp rather than Coa is a major virulence factor in S. aureus septic arthritis. vWF-deficient mice were more susceptible to bone damage in septic arthritis, especially when the Δvwb strain was used. Importantly, no difference in arthritis severity between the Δvwb and WT strains was observed in vWF-deficient mice. Collectively, we conclude that vWbp production by S. aureus enhances staphylococcal septic arthritis. IMPORTANCE Septic arthritis remains one of the most dangerous joint diseases with a rapidly progressive disease character. Despite advances in the use of antibiotics, permanent reductions in joint function due to joint deformation and deleterious contractures occur in up to 50% of patients with septic arthritis. So far, it is still largely unknown how S. aureus initiates and establishes joint infection. Here, we demonstrate that von Willebrand factor-binding protein expressed by S. aureus facilitates the initiation of septic arthritis. Such effect might be mediated through its interaction with a host factor (von Willebrand factor). Our finding contributes significantly to the full understanding of septic arthritis etiology and will pave the way for new therapeutic modalities for this devastating disease.
format	article
author	Manli Na Zhicheng Hu Majd Mohammad Mariana do Nascimento Stroparo Abukar Ali Ying Fei Anders Jarneborn Peter Verhamme Olaf Schneewind Dominique Missiakas Tao Jin
author_facet	Manli Na Zhicheng Hu Majd Mohammad Mariana do Nascimento Stroparo Abukar Ali Ying Fei Anders Jarneborn Peter Verhamme Olaf Schneewind Dominique Missiakas Tao Jin
author_sort	Manli Na
title	The Expression of von Willebrand Factor-Binding Protein Determines Joint-Invading Capacity of <named-content content-type="genus-species">Staphylococcus aureus</named-content>, a Core Mechanism of Septic Arthritis
title_short	The Expression of von Willebrand Factor-Binding Protein Determines Joint-Invading Capacity of <named-content content-type="genus-species">Staphylococcus aureus</named-content>, a Core Mechanism of Septic Arthritis
title_full	The Expression of von Willebrand Factor-Binding Protein Determines Joint-Invading Capacity of <named-content content-type="genus-species">Staphylococcus aureus</named-content>, a Core Mechanism of Septic Arthritis
title_fullStr	The Expression of von Willebrand Factor-Binding Protein Determines Joint-Invading Capacity of <named-content content-type="genus-species">Staphylococcus aureus</named-content>, a Core Mechanism of Septic Arthritis
title_full_unstemmed	The Expression of von Willebrand Factor-Binding Protein Determines Joint-Invading Capacity of <named-content content-type="genus-species">Staphylococcus aureus</named-content>, a Core Mechanism of Septic Arthritis
title_sort	expression of von willebrand factor-binding protein determines joint-invading capacity of <named-content content-type="genus-species">staphylococcus aureus</named-content>, a core mechanism of septic arthritis
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/cd913e0415954e00a89e814833bb6a1a
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The Expression of von Willebrand Factor-Binding Protein Determines Joint-Invading Capacity of <named-content content-type="genus-species">Staphylococcus aureus</named-content>, a Core Mechanism of Septic Arthritis

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