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 Pathogjournal_title
PLoS pathogensauthors
Papareddy P,Kalle M,Sørensen OE,Malmsten M,Mörgelin M,Schmidtchen Adoi
10.1371/journal.ppat.1003803subject
Has Abstractpub_date
2013-01-01 00:00:00pages
e1003803issue
12eissn
1553-7366issn
1553-7374pii
PPATHOGENS-D-13-00660journal_volume
9pub_type
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