The TFPI-2 derived peptide EDC34 improves outcome of gram-negative sepsis.

Abstract:

: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.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Papareddy P,Kalle M,Sørensen OE,Malmsten M,Mörgelin M,Schmidtchen A

doi

10.1371/journal.ppat.1003803

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

e1003803

issue

12

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-13-00660

journal_volume

9

pub_type

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