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The TFPI-2 Derived Peptide EDC34 Improves Outcome of Gram-Negative Sepsis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
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2013 (English)In: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 9, no 12, e1003803- p.Article in journal (Refereed) Published
Abstract [en]

Sepsis is characterized by a dysregulated host-pathogen response, leading to high cytokine levels, excessive coagulation and failure to eradicate invasive bacteria. Novel therapeutic strategies that address crucial pathogenetic steps during infection are urgently needed. Here, we describe novel bioactive roles and therapeutic anti-infective potential of the peptide EDC34, derived from the C-terminus of tissue factor pathway inhibitor-2 (TFPI-2). This peptide exerted direct bactericidal effects and boosted activation of the classical complement pathway including formation of antimicrobial C3a, but inhibited bacteria-induced activation of the contact system. Correspondingly, in mouse models of severe Escherichia coli and Pseudomonas aeruginosa infection, treatment with EDC34 reduced bacterial levels and lung damage. In combination with the antibiotic ceftazidime, the peptide significantly prolonged survival and reduced mortality in mice. The peptide's boosting effect on bacterial clearance paired with its inhibiting effect on excessive coagulation makes it a promising therapeutic candidate for invasive Gram-negative infections.

Place, publisher, year, edition, pages
2013. Vol. 9, no 12, e1003803- p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-219987DOI: 10.1371/journal.ppat.1003803ISI: 000330535400037OAI: diva2:703987
Available from: 2014-03-10 Created: 2014-03-09 Last updated: 2014-03-10Bibliographically approved

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