Protein C inhibitor - a novel antimicrobial agent

Malmström, ErikLund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine (author)

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.

Mörgelin, MatthiasLund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)medk-mmn (author)
Malmsten, MartinUppsala University,Uppsala universitet,Institutionen för farmaci(Swepub:lu)ma1014ma (author)
Johansson, LindaKarolinska Institutet (author)
Norrby-Teglund, AnnaKarolinska Institutet (author)
Shannon, OonaghLund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-osn (author)
Schmidtchen, ArturLund University,Lunds universitet,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Section III,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)derm-asc (author)
Meijers, Joost C M (author)
Herwald, HeikoLund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)medk-hhe (author)
InfektionsmedicinSektion III (creator_code:org_t)

In:PLoS Pathogens: Public Library of Science (PLoS)5:12, s. e1000698-1553-73661553-7374

By the author/editor: Malmström, Erik; Mörgelin, Matthi ...; Malmsten, Martin; Johansson, Linda; Norrby-Teglund, ...; Shannon, Oonagh; show more...; Schmidtchen, Art ...; Meijers, Joost C ...; Herwald, Heiko; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Microbiology in ...

By the university: Uppsala University; Lund University; Karolinska Institutet

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