Tissue Factor Pathway Inhibitor 2 Is Found in Skin and Its C-Terminal Region Encodes for Antibacterial Activity

BackgroundTissue 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 FindingsNeutrophil 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/SignificanceThe results demonstrate that the C-terminus of TFPI-2 encodes for antimicrobial activity, and may be released during wounding.