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

Houyuan Hu, Paul Armstrong, Elie Khalil, Yung-Chih Chen, Andreas Straub, Min Li, Juliana Soosairajah, Christoph Hagemeyer, Nicole Bassler, Dexing Huang, Ingo Ahrens, Guy Krippner, Elizabeth Gardiner, Karlheinz Peter

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: 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. Methodology/Principal Findings: 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 GPIbI? 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. Conclusions/Significance: 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. A? 2011 Hu et al.
Original languageEnglish
Article numbere19190
Number of pages9
JournalPLoS ONE
Volume6
Issue number4
DOIs
Publication statusPublished - 2011

Cite this

Hu, Houyuan ; Armstrong, Paul ; Khalil, Elie ; Chen, Yung-Chih ; Straub, Andreas ; Li, Min ; Soosairajah, Juliana ; Hagemeyer, Christoph ; Bassler, Nicole ; Huang, Dexing ; Ahrens, Ingo ; Krippner, Guy ; Gardiner, Elizabeth ; Peter, Karlheinz. / GPVI and GPIb alpha mediate staphylococcal superantigen-like protein 5 (SSL5) induced platelet activation and direct toward glycans as potential inhibitors. In: PLoS ONE. 2011 ; Vol. 6, No. 4.
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title = "GPVI and GPIb alpha mediate staphylococcal superantigen-like protein 5 (SSL5) induced platelet activation and direct toward glycans as potential inhibitors",
abstract = "Background: 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. Methodology/Principal Findings: 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 GPIbI? 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. Conclusions/Significance: 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. A? 2011 Hu et al.",
author = "Houyuan Hu and Paul Armstrong and Elie Khalil and Yung-Chih Chen and Andreas Straub and Min Li and Juliana Soosairajah and Christoph Hagemeyer and Nicole Bassler and Dexing Huang and Ingo Ahrens and Guy Krippner and Elizabeth Gardiner and Karlheinz Peter",
year = "2011",
doi = "10.1371/journal.pone.0019190",
language = "English",
volume = "6",
journal = "PLoS ONE",
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Hu, H, Armstrong, P, Khalil, E, Chen, Y-C, Straub, A, Li, M, Soosairajah, J, Hagemeyer, C, Bassler, N, Huang, D, Ahrens, I, Krippner, G, Gardiner, E & Peter, K 2011, 'GPVI and GPIb alpha mediate staphylococcal superantigen-like protein 5 (SSL5) induced platelet activation and direct toward glycans as potential inhibitors' PLoS ONE, vol. 6, no. 4, e19190. https://doi.org/10.1371/journal.pone.0019190

GPVI and GPIb alpha mediate staphylococcal superantigen-like protein 5 (SSL5) induced platelet activation and direct toward glycans as potential inhibitors. / Hu, Houyuan; Armstrong, Paul; Khalil, Elie; Chen, Yung-Chih; Straub, Andreas; Li, Min; Soosairajah, Juliana; Hagemeyer, Christoph; Bassler, Nicole; Huang, Dexing; Ahrens, Ingo; Krippner, Guy; Gardiner, Elizabeth; Peter, Karlheinz.

In: PLoS ONE, Vol. 6, No. 4, e19190, 2011.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - GPVI and GPIb alpha mediate staphylococcal superantigen-like protein 5 (SSL5) induced platelet activation and direct toward glycans as potential inhibitors

AU - Hu, Houyuan

AU - Armstrong, Paul

AU - Khalil, Elie

AU - Chen, Yung-Chih

AU - Straub, Andreas

AU - Li, Min

AU - Soosairajah, Juliana

AU - Hagemeyer, Christoph

AU - Bassler, Nicole

AU - Huang, Dexing

AU - Ahrens, Ingo

AU - Krippner, Guy

AU - Gardiner, Elizabeth

AU - Peter, Karlheinz

PY - 2011

Y1 - 2011

N2 - Background: 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. Methodology/Principal Findings: 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 GPIbI? 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. Conclusions/Significance: 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. A? 2011 Hu et al.

AB - Background: 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. Methodology/Principal Findings: 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 GPIbI? 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. Conclusions/Significance: 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. A? 2011 Hu et al.

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