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: Erik Malmström, Matthias Mörgelin, Martin Malmsten, Linda Johansson, Anna Norrby-Teglund, Oonagh Shannon, Artur Schmidtchen, Joost C M Meijers, Heiko Herwald
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Publicado: Public Library of Science (PLoS) 2009
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Acceso en línea:https://doaj.org/article/92aabe1548634f01850a5eaa25f6ec90
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spelling oai:doaj.org-article:92aabe1548634f01850a5eaa25f6ec902021-11-25T05:48:26ZProtein C inhibitor--a novel antimicrobial agent.1553-73661553-737410.1371/journal.ppat.1000698https://doaj.org/article/92aabe1548634f01850a5eaa25f6ec902009-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20019810/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Protein 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.Erik MalmströmMatthias MörgelinMartin MalmstenLinda JohanssonAnna Norrby-TeglundOonagh ShannonArtur SchmidtchenJoost C M MeijersHeiko HerwaldPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 5, Iss 12, p e1000698 (2009)
institution DOAJ
collection DOAJ
language EN
topic Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
spellingShingle Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
Erik Malmström
Matthias Mörgelin
Martin Malmsten
Linda Johansson
Anna Norrby-Teglund
Oonagh Shannon
Artur Schmidtchen
Joost C M Meijers
Heiko Herwald
Protein C inhibitor--a novel antimicrobial agent.
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.
format article
author Erik Malmström
Matthias Mörgelin
Martin Malmsten
Linda Johansson
Anna Norrby-Teglund
Oonagh Shannon
Artur Schmidtchen
Joost C M Meijers
Heiko Herwald
author_facet Erik Malmström
Matthias Mörgelin
Martin Malmsten
Linda Johansson
Anna Norrby-Teglund
Oonagh Shannon
Artur Schmidtchen
Joost C M Meijers
Heiko Herwald
author_sort Erik Malmström
title Protein C inhibitor--a novel antimicrobial agent.
title_short 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_sort protein c inhibitor--a novel antimicrobial agent.
publisher Public Library of Science (PLoS)
publishDate 2009
url https://doaj.org/article/92aabe1548634f01850a5eaa25f6ec90
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AT lindajohansson proteincinhibitoranovelantimicrobialagent
AT annanorrbyteglund proteincinhibitoranovelantimicrobialagent
AT oonaghshannon proteincinhibitoranovelantimicrobialagent
AT arturschmidtchen proteincinhibitoranovelantimicrobialagent
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