Title
Chicken cathelicidin-2-derived peptides with enhanced immunomodulatory and antibacterial activities against biological warfare agents
Author
Molhoek, E.M.
van Dijk, A.
Veldhuizen, E.J.A.
Dijk-Knijnenburg, H.
Mars-Groenendijk, R.H.
Boele, L.C.L.
Kaman-van Zanten, W.E.
Haagsman, H.P.
Bikker, F.J.
TNO Defensie en Veiligheid
Publication year
2010
Abstract
Host defence peptides (HDPs) are considered to be excellent candidates for the development of novel therapeutic agents. Recently, it was demonstrated that the peptide C1-15, an N-terminal segment of chicken HDP cathelicidin-2, exhibits potent antibacterial activity while lacking cytotoxicity towards eukaryotic cells. In the present study, we report that C1-15 is active against bacteria such as Bacillus anthracis and Yersinia pestis that may potentially be used by bioterrorists. Substitution of single and multiple phenylalanine (Phe) residues to tryptophan (Trp) in C1-15 resulted in variants with improved antibacterial activity against B. anthracis and Y. pestis as well as decreased salt sensitivity. In addition, these peptides exhibited enhanced neutralisation of lipopolysaccharide (LPS)-induced release of pro-inflammatory cytokines in human peripheral blood mononuclear cells (PBMCs). The antibacterial and LPS-neutralising activities of these C1-15-derived peptides are exerted at concentrations far below the concentrations that are toxic to human PBMCs. Taken together, we show that Phe → Trp substitutions in C1-15 variants enhances the antibacterial and LPS-neutralising activities against pathogenic bacteria, including those that may potentially be used as biological warfare agents. © 2010 Elsevier B.V. and the International Society of Chemotherapy.
Subject
Defence
Antibacterial activity
Biological warfare agents
Cathelicidin
Cytotoxicity
Host defence peptide
Immunomodulatory activity
To reference this document use:
http://resolver.tudelft.nl/uuid:a250ca58-d689-4ce0-bec5-2c302fe8bbd0
DOI
https://doi.org/10.1016/j.ijantimicag.2010.06.001
TNO identifier
408431
ISSN
0924-8579
Source
International Journal of Antimicrobial Agents, 36 (3), 271-274
Document type
article