Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/104805
Title: A peptide of heparin cofactor II inhibits endotoxin-mediated shock and invasive pseudomonas aeruginosa infection
Authors: Kalle, Martina
Papareddy, Praveen
Kasetty, Gopinath
van der Plas, Mariena J. A.
Mörgelin, Matthias
Malmsten, Martin
Schmidtchen, Artur
Keywords: DRNTU::Science::Biological sciences
Issue Date: 2014
Source: Kalle, M., Papareddy, P., Kasetty, G., van der Plas, M. J. A., Mörgelin, M., Malmsten, M., et al. (2014). A Peptide of Heparin Cofactor II Inhibits Endotoxin-Mediated Shock and Invasive Pseudomonas aeruginosa Infection. PLoS ONE, 9(7), e102577-.
Series/Report no.: PLoS ONE
Abstract: Sepsis and septic shock remain important medical problems with high mortality rates. Today's treatment is based mainly on using antibiotics to target the bacteria, without addressing the systemic inflammatory response, which is a major contributor to mortality in sepsis. Therefore, novel treatment options are urgently needed to counteract these complex sepsis pathologies. Heparin cofactor II (HCII) has recently been shown to be protective against Gram-negative infections. The antimicrobial effects were mapped to helices A and D of the molecule. Here we show that KYE28, a 28 amino acid long peptide representing helix D of HCII, is antimicrobial against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungus Candida albicans. Moreover, KYE28 binds to LPS and thereby reduces LPS-induced pro-inflammatory responses by decreasing NF-κB/AP-1 activation in vitro. In mouse models of LPS-induced shock, KYE28 significantly enhanced survival by dampening the pro-inflammatory cytokine response. Finally, in an invasive Pseudomonas infection model, the peptide inhibited bacterial growth and reduced the pro-inflammatory response, which lead to a significant reduction of mortality. In summary, the peptide KYE28, by simultaneously targeting bacteria and LPS-induced pro-inflammatory responses represents a novel therapeutic candidate for invasive infections.
URI: https://hdl.handle.net/10356/104805
http://hdl.handle.net/10220/20286
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0102577
Rights: © 2014 Kalle et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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