Cargando…
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...
Autores principales: | , , , |
---|---|
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 |
_version_ | 1784838214103597056 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9696029 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT walleramiek activationofhumanplateletsbystaphylococcusaureussecretedproteasestaphopaina AT birchkatie activationofhumanplateletsbystaphylococcusaureussecretedproteasestaphopaina AT gibbinsjonathanm activationofhumanplateletsbystaphylococcusaureussecretedproteasestaphopaina AT clarkesimonr activationofhumanplateletsbystaphylococcusaureussecretedproteasestaphopaina |