Tissue factor pathway inhibitor 2 is found in skin and its C-terminal region encodes for antibacterial activity

Praveen Papareddy; Martina Kalle; Ole E Sørensen; Katarina Lundqvist; Matthias Mörgelin; Martin Malmsten; Artur Schmidtchen

doi:10.1371/journal.pone.0052772

Tissue factor pathway inhibitor 2 is found in skin and its C-terminal region encodes for antibacterial activity

PLoS One. 2012;7(12):e52772. doi: 10.1371/journal.pone.0052772. Epub 2012 Dec 26.

Authors

Praveen Papareddy¹, Martina Kalle, Ole E Sørensen, Katarina Lundqvist, Matthias Mörgelin, Martin Malmsten, Artur Schmidtchen

Affiliation

¹ Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, Biomedical Center, Lund, Sweden. praveen.papareddy@med.lu.se

Abstract

Background: Tissue factor pathway inhibitor 2 (TFPI-2) is a matrix-associated serine protease inhibitor with an enigmatic function in vivo. Here, we describe that TFPI-2 is present in fibrin of wounds and also expressed in skin, where it is up-regulated upon wounding.

Methodology and principal findings: Neutrophil elastase cleaved TFPI-2, and a C-terminal fragment was found to bind to bacteria. Similarly, a prototypic peptide representing this C-terminal part, EDC34, bound to bacteria and bacterial lipopolysaccharide, and induced bacterial permeabilization. The peptide also induced leakage in artificial liposomes, and displayed a random coil conformation upon interactions with liposomes as well as lipopolysaccharide. EDC34 was antibacterial against both Gram-negative and Gram-positive bacteria in physiological buffer conditions.

Conclusions/significance: The results demonstrate that the C-terminus of TFPI-2 encodes for antimicrobial activity, and may be released during wounding.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Anti-Bacterial Agents
Antimicrobial Cationic Peptides / chemistry
Antimicrobial Cationic Peptides / metabolism
Antimicrobial Cationic Peptides / pharmacology*
Bacillus subtilis / drug effects
Candida albicans / drug effects
Disk Diffusion Antimicrobial Tests
Escherichia coli / drug effects
Escherichia coli / metabolism
Gene Expression
Glycoproteins / chemistry
Glycoproteins / metabolism
Glycoproteins / pharmacology*
Humans
Leukocyte Elastase / chemistry
Lipopolysaccharides / chemistry
Microbial Viability / drug effects
Molecular Sequence Data
Peptide Fragments / chemistry
Peptide Fragments / metabolism
Peptide Fragments / pharmacology*
Protein Binding
Protein Structure, Tertiary
Proteolysis
Pseudomonas aeruginosa / drug effects
Skin / metabolism*
Skin / pathology
Staphylococcus aureus / drug effects
Tissue Culture Techniques

Substances

Anti-Bacterial Agents
Antimicrobial Cationic Peptides
EDC34 peptide
Glycoproteins
Lipopolysaccharides
Peptide Fragments
tissue-factor-pathway inhibitor 2
Leukocyte Elastase

Grants and funding

This work was supported by grants from the Swedish Research Council (projects 2009-3378 and 2009-3009), the Welander-Finsen, Knut and Alice Wallenberg, Crafoord, Österlund, and Kock Foundations, XImmune AB, and The Swedish Government Funds for Clinical Research (ALF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.