Chicken cathelicidin-2-derived peptides with enhanced immunomodulatory and antibacterial activities against biological warfare agents

International Journal of Antimicrobial Agents
E Margo MolhoekFloris J Bikker

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 th...Continue Reading

References

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Oct 26, 2006·Chemical Biology & Drug Design·Floris J BikkerDaan Noort

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Citations

Mar 4, 2014·Pharmaceuticals·Guolong Zhang, Lakshmi T Sunkara
May 3, 2011·Veterinary Microbiology·A van DijkH P Haagsman
Mar 8, 2011·International Journal of Antimicrobial Agents·E Margo MolhoekFloris J Bikker
May 7, 2013·Developmental and Comparative Immunology·Tryntsje CuperusHenk P Haagsman
Jun 22, 2016·Developmental and Comparative Immunology·Haitham A YacoubVladimir N Uversky
Aug 17, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Daniel A SousaOctávio L Franco
Oct 27, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Cristina CamóLidia Feliu
Mar 20, 2019·Scientific Reports·Maaike R ScheenstraHenk P Haagsman
Jun 26, 2020·Frontiers in Immunology·Maaike R ScheenstraMaarten Coorens
Nov 30, 2019·Microbial Pathogenesis·Melina MartínezPaulo César Maffía
Feb 9, 2021·Journal of Peptide Science : an Official Publication of the European Peptide Society·Taoran WangChenhong Wang
Feb 14, 2021·Drug Development Research·Theodore Ebenezer LeonardAudrey Amira Crystalia
Mar 30, 2021·Poultry Science·Taichiro IshigeKei Hanzawa

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