Protein C Inhibitor—A Novel Antimicrobial Agent

PLoS Pathogens

Erik Malmström¹  Oonagh Shannon¹  Matthias Mörgelin¹  Heiko Herwald¹  Martin Malmsten²  Joost C. M. Meijers³  Artur Schmidtchen⁴  Linda Johansson⁵  Anna Norrby-Teglund⁵ 

[1] Department of Clinical Sciences, Section for Clinical and Experimental Infection Medicine, Lund University, Lund, Sweden;Department of Pharmacy, Uppsala University, Uppsala, Sweden;Departments of Vascular and Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, Lund, Sweden;Karolinska Institutet, Center for Infectious Medicine, Huddinge University Hospital, Stockholm, Sweden

关键词: Streptococcus pyogenes;    Blood plasma;    Platelets;    Streptococcal infections;    Bacteria;    Biopsy;    Antimicrobials;    Liposomes;   

DOI  :  10.1371/journal.ppat.1000698

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY