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Activation of Human Platelets by Staphylococcus aureus Secreted Protease Staphopain A

Infection by Staphylococcus aureus is the leading cause of infective endocarditis (IE). Activation of platelets by this pathogen results in their aggregation and thrombus formation which are considered to be important steps in the development and pathogenesis of IE. Here, we show that a secreted cys...

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Autores principales: Waller, Amie K., Birch, Katie, Gibbins, Jonathan M., Clarke, Simon R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9696029/
https://www.ncbi.nlm.nih.gov/pubmed/36364988
http://dx.doi.org/10.3390/pathogens11111237
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author Waller, Amie K.
Birch, Katie
Gibbins, Jonathan M.
Clarke, Simon R.
author_facet Waller, Amie K.
Birch, Katie
Gibbins, Jonathan M.
Clarke, Simon R.
author_sort Waller, Amie K.
collection PubMed
description Infection by Staphylococcus aureus is the leading cause of infective endocarditis (IE). Activation of platelets by this pathogen results in their aggregation and thrombus formation which are considered to be important steps in the development and pathogenesis of IE. Here, we show that a secreted cysteine protease, staphopain A, activates human platelets and induces their aggregation. The culture supernatant of a scpA mutant deficient in staphopain A production was reduced in its ability to trigger platelet aggregation. The platelet agonist activity of purified staphopain A was inhibited by staphostatin A, a specific inhibitor, thus implicating its protease activity in the agonism. In whole blood, using concentrations of staphopain A that were otherwise insufficient to induce platelet aggregation, increased binding to collagen and thrombus formation was observed. Using antagonists specific to protease-activated receptors 1 and 4, we demonstrate their role in mediating staphopain A induced platelet activation.
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spelling pubmed-96960292022-11-26 Activation of Human Platelets by Staphylococcus aureus Secreted Protease Staphopain A Waller, Amie K. Birch, Katie Gibbins, Jonathan M. Clarke, Simon R. Pathogens Article Infection by Staphylococcus aureus is the leading cause of infective endocarditis (IE). Activation of platelets by this pathogen results in their aggregation and thrombus formation which are considered to be important steps in the development and pathogenesis of IE. Here, we show that a secreted cysteine protease, staphopain A, activates human platelets and induces their aggregation. The culture supernatant of a scpA mutant deficient in staphopain A production was reduced in its ability to trigger platelet aggregation. The platelet agonist activity of purified staphopain A was inhibited by staphostatin A, a specific inhibitor, thus implicating its protease activity in the agonism. In whole blood, using concentrations of staphopain A that were otherwise insufficient to induce platelet aggregation, increased binding to collagen and thrombus formation was observed. Using antagonists specific to protease-activated receptors 1 and 4, we demonstrate their role in mediating staphopain A induced platelet activation. MDPI 2022-10-26 /pmc/articles/PMC9696029/ /pubmed/36364988 http://dx.doi.org/10.3390/pathogens11111237 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Waller, Amie K.
Birch, Katie
Gibbins, Jonathan M.
Clarke, Simon R.
Activation of Human Platelets by Staphylococcus aureus Secreted Protease Staphopain A
title Activation of Human Platelets by Staphylococcus aureus Secreted Protease Staphopain A
title_full Activation of Human Platelets by Staphylococcus aureus Secreted Protease Staphopain A
title_fullStr Activation of Human Platelets by Staphylococcus aureus Secreted Protease Staphopain A
title_full_unstemmed Activation of Human Platelets by Staphylococcus aureus Secreted Protease Staphopain A
title_short Activation of Human Platelets by Staphylococcus aureus Secreted Protease Staphopain A
title_sort activation of human platelets by staphylococcus aureus secreted protease staphopain a
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9696029/
https://www.ncbi.nlm.nih.gov/pubmed/36364988
http://dx.doi.org/10.3390/pathogens11111237
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