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Preventing Staphylococcus aureus Sepsis through the Inhibition of Its Agglutination in Blood

Staphylococcus aureus infection is a frequent cause of sepsis in humans, a disease associated with high mortality and without specific intervention. When suspended in human or animal plasma, staphylococci are known to agglutinate, however the bacterial factors responsible for agglutination and their...

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Autores principales: McAdow, Molly, Kim, Hwan Keun, DeDent, Andrea C., Hendrickx, Antoni P. A., Schneewind, Olaf, Missiakas, Dominique M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3197598/
https://www.ncbi.nlm.nih.gov/pubmed/22028651
http://dx.doi.org/10.1371/journal.ppat.1002307
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author McAdow, Molly
Kim, Hwan Keun
DeDent, Andrea C.
Hendrickx, Antoni P. A.
Schneewind, Olaf
Missiakas, Dominique M.
author_facet McAdow, Molly
Kim, Hwan Keun
DeDent, Andrea C.
Hendrickx, Antoni P. A.
Schneewind, Olaf
Missiakas, Dominique M.
author_sort McAdow, Molly
collection PubMed
description Staphylococcus aureus infection is a frequent cause of sepsis in humans, a disease associated with high mortality and without specific intervention. When suspended in human or animal plasma, staphylococci are known to agglutinate, however the bacterial factors responsible for agglutination and their possible contribution to disease pathogenesis have not yet been revealed. Using a mouse model for S. aureus sepsis, we report here that staphylococcal agglutination in blood was associated with a lethal outcome of this disease. Three secreted products of staphylococci - coagulase (Coa), von Willebrand factor binding protein (vWbp) and clumping factor (ClfA) – were required for agglutination. Coa and vWbp activate prothrombin to cleave fibrinogen, whereas ClfA allowed staphylococci to associate with the resulting fibrin cables. All three virulence genes promoted the formation of thromboembolic lesions in heart tissues. S. aureus agglutination could be disrupted and the lethal outcome of sepsis could be prevented by combining dabigatran-etexilate treatment, which blocked Coa and vWbp activity, with antibodies specific for ClfA. Together these results suggest that the combined administration of direct thrombin inhibitors and ClfA-antibodies that block S. aureus agglutination with fibrin may be useful for the prevention of staphylococcal sepsis in humans.
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spelling pubmed-31975982011-10-25 Preventing Staphylococcus aureus Sepsis through the Inhibition of Its Agglutination in Blood McAdow, Molly Kim, Hwan Keun DeDent, Andrea C. Hendrickx, Antoni P. A. Schneewind, Olaf Missiakas, Dominique M. PLoS Pathog Research Article Staphylococcus aureus infection is a frequent cause of sepsis in humans, a disease associated with high mortality and without specific intervention. When suspended in human or animal plasma, staphylococci are known to agglutinate, however the bacterial factors responsible for agglutination and their possible contribution to disease pathogenesis have not yet been revealed. Using a mouse model for S. aureus sepsis, we report here that staphylococcal agglutination in blood was associated with a lethal outcome of this disease. Three secreted products of staphylococci - coagulase (Coa), von Willebrand factor binding protein (vWbp) and clumping factor (ClfA) – were required for agglutination. Coa and vWbp activate prothrombin to cleave fibrinogen, whereas ClfA allowed staphylococci to associate with the resulting fibrin cables. All three virulence genes promoted the formation of thromboembolic lesions in heart tissues. S. aureus agglutination could be disrupted and the lethal outcome of sepsis could be prevented by combining dabigatran-etexilate treatment, which blocked Coa and vWbp activity, with antibodies specific for ClfA. Together these results suggest that the combined administration of direct thrombin inhibitors and ClfA-antibodies that block S. aureus agglutination with fibrin may be useful for the prevention of staphylococcal sepsis in humans. Public Library of Science 2011-10-20 /pmc/articles/PMC3197598/ /pubmed/22028651 http://dx.doi.org/10.1371/journal.ppat.1002307 Text en McAdow et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
McAdow, Molly
Kim, Hwan Keun
DeDent, Andrea C.
Hendrickx, Antoni P. A.
Schneewind, Olaf
Missiakas, Dominique M.
Preventing Staphylococcus aureus Sepsis through the Inhibition of Its Agglutination in Blood
title Preventing Staphylococcus aureus Sepsis through the Inhibition of Its Agglutination in Blood
title_full Preventing Staphylococcus aureus Sepsis through the Inhibition of Its Agglutination in Blood
title_fullStr Preventing Staphylococcus aureus Sepsis through the Inhibition of Its Agglutination in Blood
title_full_unstemmed Preventing Staphylococcus aureus Sepsis through the Inhibition of Its Agglutination in Blood
title_short Preventing Staphylococcus aureus Sepsis through the Inhibition of Its Agglutination in Blood
title_sort preventing staphylococcus aureus sepsis through the inhibition of its agglutination in blood
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3197598/
https://www.ncbi.nlm.nih.gov/pubmed/22028651
http://dx.doi.org/10.1371/journal.ppat.1002307
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