vhp Is a Fibrinogen-Binding Protein Related to vWbp in <named-content content-type="genus-species">Staphylococcus aureus</named-content>

ABSTRACT Staphylococcus aureus can target a variety of tissues, causing life-threatening infections. The basis for this diversity stems from the microorganism’s ability to spread in the vascular system throughout the body. To survive in blood, S. aureus coats itself with a fibrinogen (Fg)/fibrin shi...

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Autores principales:	Sheila Thomas, Srishtee Arora, Wen Liu, Kelly Churion, You Wu, Magnus Höök
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2021
Materias:	Staphylococcus aureus fibrinogen-binding proteins vhp vWbp homolog Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/81919111e9994243800b59f15662663f
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spelling	oai:doaj.org-article:81919111e9994243800b59f15662663f2021-11-10T18:37:51Zvhp Is a Fibrinogen-Binding Protein Related to vWbp in <named-content content-type="genus-species">Staphylococcus aureus</named-content>10.1128/mBio.01167-212150-7511https://doaj.org/article/81919111e9994243800b59f15662663f2021-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01167-21https://doaj.org/toc/2150-7511ABSTRACT Staphylococcus aureus can target a variety of tissues, causing life-threatening infections. The basis for this diversity stems from the microorganism’s ability to spread in the vascular system throughout the body. To survive in blood, S. aureus coats itself with a fibrinogen (Fg)/fibrin shield. The protective shield is assembled by the coordinated actions of a number of Fg-binding bacterial proteins that manipulate the host’s blood coagulation system. Several of the Fg binders appear redundant, sharing similar functional motifs. This observation led us to screen for the presence of novel proteins with significant amino acid identities to von Willebrand factor-binding protein (vWbp), a key component in the shield assembly machinery. One identified protein showed significant sequence identity with the C-terminal region of vWbp, and we consequently named it vWbp homologous protein (vhp). The vhp gene lies within a cluster of genes that encode other virulence factors in S. aureus. Although each isolate only contains one copy of the vhp gene, S. aureus has at least three distinct alleles, vhpA, B, and C, that are present in the core genome. All three vhp isoforms bind Fg with high affinity, targeting a site located in the D fragment of Fg. We further identified an ∼79 amino acid-long, conserved segment within the C-terminal region of vWbp that shares high sequence identities (54 to 67%) with the vhps and binds soluble Fg with high affinity. Further analysis of this conserved motif and the intact vhps revealed intriguing differences in the Fg binding behavior, perhaps suggesting that these proteins have similar but discrete functions in the shield assembly. IMPORTANCE The life-threatening diseases caused by multidrug-resistant Staphylococcus aureus strains are a worldwide medical problem due to treatment limitations and the lack of an effective vaccine. The ability of S. aureus to coat itself with a protective fibrinogen (Fg)/fibrin shield allows the organism to survive in blood and to disseminate and cause invasive diseases. This process represents a promising target for novel antistaphylococcal treatment strategies but is incompletely understood. S. aureus expresses a number of Fg-binding proteins. Some of these proteins have apparently redundant functions. Proteins with similar functions often share a structural or functional motif with each other. In this study, we identified a protein homologous to the C-terminal of von Willebrand factor-binding protein (vWbp), a key contributor in the Fg shield assembly that also binds Fg. Further analysis allowed us to identify a common Fg-binding motif.Sheila ThomasSrishtee AroraWen LiuKelly ChurionYou WuMagnus HöökAmerican Society for MicrobiologyarticleStaphylococcus aureusfibrinogen-binding proteinsvhpvWbp homologMicrobiologyQR1-502ENmBio, Vol 12, Iss 4 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Staphylococcus aureus fibrinogen-binding proteins vhp vWbp homolog Microbiology QR1-502
spellingShingle	Staphylococcus aureus fibrinogen-binding proteins vhp vWbp homolog Microbiology QR1-502 Sheila Thomas Srishtee Arora Wen Liu Kelly Churion You Wu Magnus Höök vhp Is a Fibrinogen-Binding Protein Related to vWbp in <named-content content-type="genus-species">Staphylococcus aureus</named-content>
description	ABSTRACT Staphylococcus aureus can target a variety of tissues, causing life-threatening infections. The basis for this diversity stems from the microorganism’s ability to spread in the vascular system throughout the body. To survive in blood, S. aureus coats itself with a fibrinogen (Fg)/fibrin shield. The protective shield is assembled by the coordinated actions of a number of Fg-binding bacterial proteins that manipulate the host’s blood coagulation system. Several of the Fg binders appear redundant, sharing similar functional motifs. This observation led us to screen for the presence of novel proteins with significant amino acid identities to von Willebrand factor-binding protein (vWbp), a key component in the shield assembly machinery. One identified protein showed significant sequence identity with the C-terminal region of vWbp, and we consequently named it vWbp homologous protein (vhp). The vhp gene lies within a cluster of genes that encode other virulence factors in S. aureus. Although each isolate only contains one copy of the vhp gene, S. aureus has at least three distinct alleles, vhpA, B, and C, that are present in the core genome. All three vhp isoforms bind Fg with high affinity, targeting a site located in the D fragment of Fg. We further identified an ∼79 amino acid-long, conserved segment within the C-terminal region of vWbp that shares high sequence identities (54 to 67%) with the vhps and binds soluble Fg with high affinity. Further analysis of this conserved motif and the intact vhps revealed intriguing differences in the Fg binding behavior, perhaps suggesting that these proteins have similar but discrete functions in the shield assembly. IMPORTANCE The life-threatening diseases caused by multidrug-resistant Staphylococcus aureus strains are a worldwide medical problem due to treatment limitations and the lack of an effective vaccine. The ability of S. aureus to coat itself with a protective fibrinogen (Fg)/fibrin shield allows the organism to survive in blood and to disseminate and cause invasive diseases. This process represents a promising target for novel antistaphylococcal treatment strategies but is incompletely understood. S. aureus expresses a number of Fg-binding proteins. Some of these proteins have apparently redundant functions. Proteins with similar functions often share a structural or functional motif with each other. In this study, we identified a protein homologous to the C-terminal of von Willebrand factor-binding protein (vWbp), a key contributor in the Fg shield assembly that also binds Fg. Further analysis allowed us to identify a common Fg-binding motif.
format	article
author	Sheila Thomas Srishtee Arora Wen Liu Kelly Churion You Wu Magnus Höök
author_facet	Sheila Thomas Srishtee Arora Wen Liu Kelly Churion You Wu Magnus Höök
author_sort	Sheila Thomas
title	vhp Is a Fibrinogen-Binding Protein Related to vWbp in <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_short	vhp Is a Fibrinogen-Binding Protein Related to vWbp in <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_full	vhp Is a Fibrinogen-Binding Protein Related to vWbp in <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_fullStr	vhp Is a Fibrinogen-Binding Protein Related to vWbp in <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_full_unstemmed	vhp Is a Fibrinogen-Binding Protein Related to vWbp in <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_sort	vhp is a fibrinogen-binding protein related to vwbp in <named-content content-type="genus-species">staphylococcus aureus</named-content>
publisher	American Society for Microbiology
publishDate	2021
url	https://doaj.org/article/81919111e9994243800b59f15662663f
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vhp Is a Fibrinogen-Binding Protein Related to vWbp in <named-content content-type="genus-species">Staphylococcus aureus</named-content>

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