Thrombin-Derived C-Terminal Peptide Reduces -Induced Inflammation and Infection and .

Infections due to the opportunistic fungus Candida have been on the rise in the last decades, especially in immunocompromised individuals and hospital settings. Unfortunately, the treatments available today are limited. Thrombin-derived C-terminal peptide (TCP-25) is an antimicrobial peptide (AMP) with antibacterial and immunomodulatory effects. In this work, we, for the first time, demonstrate the ability of TCP-25 ability to counteract Candida and . Using a combination of viable count assay (VCA), radial diffusion assay (RDA), and fluorescence and transmission electron microscopy analyses, TCP-25 was found to exert a direct fungicidal activity. An inhibitory activity of TCP-25 on NF-κB activation induced by both zymosan alone and heat-killed C. albicans was demonstrated using THP-1 cells, and using NF-κB reporter mice. Moreover, the immunomodulatory property of TCP-25 was further substantiated by analyzing cytokine responses in human blood stimulated with zymosan, and employing a zymosan-induced peritonitis model in C57BL/6 mice. The therapeutic potential of TCP-25 was demonstrated in mice infected with luminescent C. albicans. Finally, the binding between TCP-25 and zymosan was investigated using circular dichroism spectroscopy and intrinsic fluorescence analysis. Taken together, our results show that TCP-25 has a dual function by inhibiting as well as the associated zymosan-induced inflammation. The latter function is accompanied by a change in secondary structure upon binding to zymosan. TCP-25, therefore, shows promise as a novel drug candidate against infections.