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Protein C Inhibitor—A Novel Antimicrobial Agent

Protein C inhibitor (PCI) is a heparin-binding serine proteinase inhibitor belonging to the family of serpin proteins. Here we describe that PCI exerts broad antimicrobial activity against bacterial pathogens. This ability is mediated by the interaction of PCI with lipid membranes, which subsequentl...

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Autores principales: Malmström, Erik, Mörgelin, Matthias, Malmsten, Martin, Johansson, Linda, Norrby-Teglund, Anna, Shannon, Oonagh, Schmidtchen, Artur, Meijers, Joost C. M., Herwald, Heiko
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2788422/
https://www.ncbi.nlm.nih.gov/pubmed/20019810
http://dx.doi.org/10.1371/journal.ppat.1000698
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author Malmström, Erik
Mörgelin, Matthias
Malmsten, Martin
Johansson, Linda
Norrby-Teglund, Anna
Shannon, Oonagh
Schmidtchen, Artur
Meijers, Joost C. M.
Herwald, Heiko
author_facet Malmström, Erik
Mörgelin, Matthias
Malmsten, Martin
Johansson, Linda
Norrby-Teglund, Anna
Shannon, Oonagh
Schmidtchen, Artur
Meijers, Joost C. M.
Herwald, Heiko
author_sort Malmström, Erik
collection PubMed
description Protein C inhibitor (PCI) is a heparin-binding serine proteinase inhibitor belonging to the family of serpin proteins. Here we describe that PCI exerts broad antimicrobial activity against bacterial pathogens. This ability is mediated by the interaction of PCI with lipid membranes, which subsequently leads to their permeabilization. As shown by negative staining electron microscopy, treatment of Escherichia coli or Streptococcus pyogenes bacteria with PCI triggers membrane disruption followed by the efflux of bacterial cytosolic contents and bacterial killing. The antimicrobial activity of PCI is located to the heparin-binding site of the protein and a peptide spanning this region was found to mimic the antimicrobial activity of PCI, without causing lysis or membrane destruction of eukaryotic cells. Finally, we show that platelets can assemble PCI on their surface upon activation. As platelets are recruited to the site of a bacterial infection, these results may explain our finding that PCI levels are increased in tissue biopsies from patients suffering from necrotizing fasciitis caused by S. pyogenes. Taken together, our data describe a new function for PCI in innate immunity.
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spelling pubmed-27884222009-12-18 Protein C Inhibitor—A Novel Antimicrobial Agent Malmström, Erik Mörgelin, Matthias Malmsten, Martin Johansson, Linda Norrby-Teglund, Anna Shannon, Oonagh Schmidtchen, Artur Meijers, Joost C. M. Herwald, Heiko PLoS Pathog Research Article Protein C inhibitor (PCI) is a heparin-binding serine proteinase inhibitor belonging to the family of serpin proteins. Here we describe that PCI exerts broad antimicrobial activity against bacterial pathogens. This ability is mediated by the interaction of PCI with lipid membranes, which subsequently leads to their permeabilization. As shown by negative staining electron microscopy, treatment of Escherichia coli or Streptococcus pyogenes bacteria with PCI triggers membrane disruption followed by the efflux of bacterial cytosolic contents and bacterial killing. The antimicrobial activity of PCI is located to the heparin-binding site of the protein and a peptide spanning this region was found to mimic the antimicrobial activity of PCI, without causing lysis or membrane destruction of eukaryotic cells. Finally, we show that platelets can assemble PCI on their surface upon activation. As platelets are recruited to the site of a bacterial infection, these results may explain our finding that PCI levels are increased in tissue biopsies from patients suffering from necrotizing fasciitis caused by S. pyogenes. Taken together, our data describe a new function for PCI in innate immunity. Public Library of Science 2009-12-18 /pmc/articles/PMC2788422/ /pubmed/20019810 http://dx.doi.org/10.1371/journal.ppat.1000698 Text en Malmström 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
Malmström, Erik
Mörgelin, Matthias
Malmsten, Martin
Johansson, Linda
Norrby-Teglund, Anna
Shannon, Oonagh
Schmidtchen, Artur
Meijers, Joost C. M.
Herwald, Heiko
Protein C Inhibitor—A Novel Antimicrobial Agent
title Protein C Inhibitor—A Novel Antimicrobial Agent
title_full Protein C Inhibitor—A Novel Antimicrobial Agent
title_fullStr Protein C Inhibitor—A Novel Antimicrobial Agent
title_full_unstemmed Protein C Inhibitor—A Novel Antimicrobial Agent
title_short Protein C Inhibitor—A Novel Antimicrobial Agent
title_sort protein c inhibitor—a novel antimicrobial agent
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2788422/
https://www.ncbi.nlm.nih.gov/pubmed/20019810
http://dx.doi.org/10.1371/journal.ppat.1000698
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