Protein C inhibitor--a novel antimicrobial agent.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1523498
- author
- Malmström, Erik
LU
; Mörgelin, Matthias
LU
; Malmsten, Martin
LU
; Johansson, Linda
; Norrby-Teglund, Anna
; Shannon, Oonagh
LU
; Schmidtchen, Artur
LU
; Meijers, Joost C M
and Herwald, Heiko
LU
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS Pathogens
- volume
- 5
- issue
- 12
- publisher
- Public Library of Science (PLoS)
- 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
- 2016-04-01 12:38:20
- date last changed
- 2022-03-29 03:35:59
@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 (PLoS)}}, series = {{PLoS Pathogens}}, title = {{Protein C inhibitor--a novel antimicrobial agent.}}, url = {{https://lup.lub.lu.se/search/files/3004906/1550860.pdf}}, doi = {{10.1371/journal.ppat.1000698}}, volume = {{5}}, year = {{2009}}, }