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The TFPI-2 Derived Peptide EDC34 Improves Outcome of Gram-Negative Sepsis.

Papareddy, Praveen LU ; Kalle, Martina LU ; Sørensen, Ole E LU ; Malmsten, Martin; Mörgelin, Matthias LU and Schmidtchen, Artur LU (2013) In PLoS Pathogens 9(12).
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS Pathogens
volume
9
issue
12
publisher
Public Library of Science
external identifiers
  • pmid:24339780
  • wos:000330535400037
  • scopus:84882239573
ISSN
1553-7366
DOI
10.1371/journal.ppat.1003803
language
English
LU publication?
yes
id
d44ea8a3-70b0-449f-8fda-938e33c9c369 (old id 4223655)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24339780?dopt=Abstract
date added to LUP
2014-01-04 18:34:10
date last changed
2019-08-28 01:09:20
@article{d44ea8a3-70b0-449f-8fda-938e33c9c369,
  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.},
  articleno    = {e1003803},
  author       = {Papareddy, Praveen and Kalle, Martina and Sørensen, Ole E and Malmsten, Martin and Mörgelin, Matthias and Schmidtchen, Artur},
  issn         = {1553-7366},
  language     = {eng},
  number       = {12},
  publisher    = {Public Library of Science},
  series       = {PLoS Pathogens},
  title        = {The TFPI-2 Derived Peptide EDC34 Improves Outcome of Gram-Negative Sepsis.},
  url          = {http://dx.doi.org/10.1371/journal.ppat.1003803},
  volume       = {9},
  year         = {2013},
}