Table of Contents
International Journal of Peptides
Volume 2011, Article ID 761037, 11 pages
Research Article

Antifungal Activities of Peptides Derived from Domain 5 of High-Molecular-Weight Kininogen

1Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, 221 84 Lund, Sweden
2Department of Pharmacy, Uppsala University, 751 23 Uppsala, Sweden

Received 1 April 2011; Accepted 16 June 2011

Academic Editor: Manuela Raffatellu

Copyright © 2011 Andreas Sonesson et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


In both immunocompromised and immunocompetent patients, Candida and Malassezia are causing or triggering clinical manifestations such as cutaneous infections and atopic eczema. The innate immune system provides rapid responses to microbial invaders, without requiring prior stimulation, through a sophisticated system of antimicrobial peptides (AMPs). High molecular weight kininogen (HMWK) and components of the contact system have previously been reported to bind to Candida and other pathogens, leading to activation of the contact system. A cutaneous Candida infection is characterized by an accumulation of neutrophils, leading to an inflammatory response and release of enzymatically active substances. In the present study we demonstrate that antifungal peptide fragments are generated through proteolytic degradation of HMWK. The recombinant domain 5 (rD5) of HMWK, D5-derived peptides, as well as hydrophobically modified D5-derived peptides efficiently killed Candida and Malassezia. Furthermore, the antifungal activity of modified peptides was studied at physiological conditions. Binding of a D5-derived peptide, HKH20 (His479-His498), to the fungal cell membrane was visualized by fluorescence microscopy. Our data disclose a novel antifungal activity of D5-derived peptides and also show that proteolytic cleavage of HMWK results in fragments exerting antifungal activity. Of therapeutic interest is that structurally modified peptides show an enhanced antifungal activity.