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Protein C inhibitor--a novel antimicrobial agent.

Malmström, Erik LU ; Mörgelin, Matthias LU ; Malmsten, Martin; Johansson, Linda; Norrby-Teglund, Anna; Shannon, Oonagh LU ; Schmidtchen, Artur LU ; Meijers, Joost C M and Herwald, Heiko LU (2009) In PLoS Pathogens 5(12).
Abstract
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,... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS Pathogens
volume
5
issue
12
publisher
Public Library of Science
external identifiers
  • wos:000274227000022
  • pmid:20019810
  • scopus:74549135127
ISSN
1553-7366
DOI
10.1371/journal.ppat.1000698
language
English
LU publication?
yes
id
493522d2-e695-4f44-94e4-b6970c741f22 (old id 1523498)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20019810?dopt=Abstract
date added to LUP
2010-01-12 13:00:42
date last changed
2017-11-19 03:40:34
@article{493522d2-e695-4f44-94e4-b6970c741f22,
  abstract     = {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.},
  author       = {Malmström, Erik and Mörgelin, Matthias and Malmsten, Martin and Johansson, Linda and Norrby-Teglund, Anna and Shannon, Oonagh and Schmidtchen, Artur and Meijers, Joost C M and Herwald, Heiko},
  issn         = {1553-7366},
  language     = {eng},
  number       = {12},
  publisher    = {Public Library of Science},
  series       = {PLoS Pathogens},
  title        = {Protein C inhibitor--a novel antimicrobial agent.},
  url          = {http://dx.doi.org/10.1371/journal.ppat.1000698},
  volume       = {5},
  year         = {2009},
}