NLF20: an antimicrobial peptide with therapeutic potential against invasive Pseudomonas aeruginosa infection
2016 (English)In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 71, no 1, 170-180 p.Article in journal (Refereed) PublishedText
Objectives:Increasing resistance to antibiotics makes antimicrobial peptides interesting as novel therapeutics. Here, we report on studies of the peptide NLF20 (NLFRKLTHRLFRRNFGYTLR), corresponding to an epitope of the D helix of heparin cofactor II (HCII), a plasma protein mediating bacterial clearance. Methods: Peptide effects were evaluated by a combination of in vitro and in vivo methods, including antibacterial, anti-inflammatory and cytotoxicity assays, fluorescence and electron microscopy, and experimental models of endotoxin shock and Pseudomonas aeruginosa sepsis. Results: The results showed that NLF20 displayed potent antimicrobial effects against the Gram-negative bacteria Escherichia coli and P. aeruginosa, the Gram-positive Bacillus subtilis and Staphylococcus aureus and the fungi Candida albicans and Candida parapsilosis. Importantly, this antimicrobial effect was retained in human blood, particularly for P. aeruginosa. Fluorescence and electron microscopy studies showed that the peptide exerted membrane-breaking effects. In an animal model of P. aeruginosa sepsis, NLF20 reduced bacterial levels, resulting in improved survival. Reduced mortality was also observed in experimental animal models of endotoxin shock, which was paralleled with modulated IFN-gamma, IL-10 and coagulation responses. Conclusions: Together, these results indicate that functional epitopes of HCII may have therapeutic potential against bacterial infection.
Place, publisher, year, edition, pages
2016. Vol. 71, no 1, 170-180 p.
IdentifiersURN: urn:nbn:se:uu:diva-282654DOI: 10.1093/jac/dkv322ISI: 000371238100026OAI: oai:DiVA.org:uu-282654DiVA: diva2:917444
FunderSwedish Research Council, 2012-1842, 2012-1883Knut and Alice Wallenberg FoundationThe Crafoord FoundationTorsten Söderbergs stiftelseSwedish Foundation for Strategic Research