GPVI and GPIbα mediate staphylococcal superantigen-like protein 5 (SSL5) induced platelet activation and direct toward glycans as potential inhibitors.

<h4>Background</h4>Staphylococcus aureus (S. aureus) is a common pathogen capable of causing life-threatening infections. Staphylococcal superantigen-like protein 5 (SSL5) has recently been shown to bind to platelet glycoproteins and induce platelet activation. This study investigates fu...

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Autores principales:	Houyuan Hu, Paul C J Armstrong, Elie Khalil, Yung-Chih Chen, Andreas Straub, Min Li, Juliana Soosairajah, Christoph E Hagemeyer, Nicole Bassler, Dexing Huang, Ingo Ahrens, Guy Krippner, Elizabeth Gardiner, Karlheinz Peter
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/750bca4deeff4d52ad3d733c149b7921
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spelling	oai:doaj.org-article:750bca4deeff4d52ad3d733c149b79212021-11-18T06:55:00ZGPVI and GPIbα mediate staphylococcal superantigen-like protein 5 (SSL5) induced platelet activation and direct toward glycans as potential inhibitors.1932-620310.1371/journal.pone.0019190https://doaj.org/article/750bca4deeff4d52ad3d733c149b79212011-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21552524/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Staphylococcus aureus (S. aureus) is a common pathogen capable of causing life-threatening infections. Staphylococcal superantigen-like protein 5 (SSL5) has recently been shown to bind to platelet glycoproteins and induce platelet activation. This study investigates further the interaction between SSL5 and platelet glycoproteins. Moreover, using a glycan discovery approach, we aim to identify potential glycans to therapeutically target this interaction and prevent SSL5-induced effects.<h4>Methodology/principal findings</h4>In addition to platelet activation experiments, flow cytometry, immunoprecipitation, surface plasmon resonance and a glycan binding array, were used to identify specific SSL5 binding regions and mediators. We independently confirm SSL5 to interact with platelets via GPIbα and identify the sulphated-tyrosine residues as an important region for SSL5 binding. We also identify the novel direct interaction between SSL5 and the platelet collagen receptor GPVI. Together, these receptors offer one mechanistic explanation for the unique functional influences SSL5 exerts on platelets. A role for specific families of platelet glycans in mediating SSL5-platelet interactions was also discovered and used to identify and demonstrate effectiveness of potential glycan based inhibitors in vitro.<h4>Conclusions/significance</h4>These findings further elucidate the functional interactions between SSL5 and platelets, including the novel finding of a role for the GPVI receptor. We demonstrate efficacy of possible glycan-based approaches to inhibit the SSL5-induced platelet activation. Our data warrant further work to prove SSL5-platelet effects in vivo.Houyuan HuPaul C J ArmstrongElie KhalilYung-Chih ChenAndreas StraubMin LiJuliana SoosairajahChristoph E HagemeyerNicole BasslerDexing HuangIngo AhrensGuy KrippnerElizabeth GardinerKarlheinz PeterPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 4, p e19190 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Houyuan Hu Paul C J Armstrong Elie Khalil Yung-Chih Chen Andreas Straub Min Li Juliana Soosairajah Christoph E Hagemeyer Nicole Bassler Dexing Huang Ingo Ahrens Guy Krippner Elizabeth Gardiner Karlheinz Peter GPVI and GPIbα mediate staphylococcal superantigen-like protein 5 (SSL5) induced platelet activation and direct toward glycans as potential inhibitors.
description	<h4>Background</h4>Staphylococcus aureus (S. aureus) is a common pathogen capable of causing life-threatening infections. Staphylococcal superantigen-like protein 5 (SSL5) has recently been shown to bind to platelet glycoproteins and induce platelet activation. This study investigates further the interaction between SSL5 and platelet glycoproteins. Moreover, using a glycan discovery approach, we aim to identify potential glycans to therapeutically target this interaction and prevent SSL5-induced effects.<h4>Methodology/principal findings</h4>In addition to platelet activation experiments, flow cytometry, immunoprecipitation, surface plasmon resonance and a glycan binding array, were used to identify specific SSL5 binding regions and mediators. We independently confirm SSL5 to interact with platelets via GPIbα and identify the sulphated-tyrosine residues as an important region for SSL5 binding. We also identify the novel direct interaction between SSL5 and the platelet collagen receptor GPVI. Together, these receptors offer one mechanistic explanation for the unique functional influences SSL5 exerts on platelets. A role for specific families of platelet glycans in mediating SSL5-platelet interactions was also discovered and used to identify and demonstrate effectiveness of potential glycan based inhibitors in vitro.<h4>Conclusions/significance</h4>These findings further elucidate the functional interactions between SSL5 and platelets, including the novel finding of a role for the GPVI receptor. We demonstrate efficacy of possible glycan-based approaches to inhibit the SSL5-induced platelet activation. Our data warrant further work to prove SSL5-platelet effects in vivo.
format	article
author	Houyuan Hu Paul C J Armstrong Elie Khalil Yung-Chih Chen Andreas Straub Min Li Juliana Soosairajah Christoph E Hagemeyer Nicole Bassler Dexing Huang Ingo Ahrens Guy Krippner Elizabeth Gardiner Karlheinz Peter
author_facet	Houyuan Hu Paul C J Armstrong Elie Khalil Yung-Chih Chen Andreas Straub Min Li Juliana Soosairajah Christoph E Hagemeyer Nicole Bassler Dexing Huang Ingo Ahrens Guy Krippner Elizabeth Gardiner Karlheinz Peter
author_sort	Houyuan Hu
title	GPVI and GPIbα mediate staphylococcal superantigen-like protein 5 (SSL5) induced platelet activation and direct toward glycans as potential inhibitors.
title_short	GPVI and GPIbα mediate staphylococcal superantigen-like protein 5 (SSL5) induced platelet activation and direct toward glycans as potential inhibitors.
title_full	GPVI and GPIbα mediate staphylococcal superantigen-like protein 5 (SSL5) induced platelet activation and direct toward glycans as potential inhibitors.
title_fullStr	GPVI and GPIbα mediate staphylococcal superantigen-like protein 5 (SSL5) induced platelet activation and direct toward glycans as potential inhibitors.
title_full_unstemmed	GPVI and GPIbα mediate staphylococcal superantigen-like protein 5 (SSL5) induced platelet activation and direct toward glycans as potential inhibitors.
title_sort	gpvi and gpibα mediate staphylococcal superantigen-like protein 5 (ssl5) induced platelet activation and direct toward glycans as potential inhibitors.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/750bca4deeff4d52ad3d733c149b7921
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GPVI and GPIbα mediate staphylococcal superantigen-like protein 5 (SSL5) induced platelet activation and direct toward glycans as potential inhibitors.

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