Proteolytic Degradation of reduced Human Beta Defensin 1 generates a Novel Antibiotic Octapeptide

Microbial resistance against clinical used antibiotics is on the rise. Accordingly, there is a high demand for new innovative antimicrobial strategies. The host-defense peptide human beta-defensin 1 (hBD-1) is produced continuously by epithelial cells and exhibits compelling antimicrobial activity a...

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Bibliographic Details
Published in:Scientific reports 2019-03, Vol.9 (1), p.3640-3640, Article 3640
Main Authors: Wendler, Judith, Schroeder, Bjoern O., Ehmann, Dirk, Koeninger, Louis, Mailänder-Sánchez, Daniela, Lemberg, Christina, Wanner, Stephanie, Schaller, Martin, Stange, Eduard F., Malek, Nisar P., Weidenmaier, Christopher, LeibundGut-Landmann, Salomé, Wehkamp, Jan
Format: Article
Language:English
Subjects:
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Amino acids
Antibiotic resistance
Antibiotics
Antimicrobial activity
Antimicrobial agents
Biodegradation
Candida albicans
D-Amino acids
E coli
Epithelial cells
Humanities and Social Sciences
Microorganisms
multidisciplinary
Peptides
Proteolysis
Science
Science (multidisciplinary)
Secretions
Therapeutic applications
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Summary:Microbial resistance against clinical used antibiotics is on the rise. Accordingly, there is a high demand for new innovative antimicrobial strategies. The host-defense peptide human beta-defensin 1 (hBD-1) is produced continuously by epithelial cells and exhibits compelling antimicrobial activity after reduction of its disulphide bridges. Here we report that proteolysis of reduced hBD-1 by gastrointestinal proteases as well as human duodenal secretions produces an eight-amino acid carboxy-terminal fragment. The generated octapeptide retains antibiotic activity, yet with distinct characteristics differing from the full-length peptide. We modified the octapeptide by stabilizing its termini and by using non-natural D-amino acids. The native and modified peptide variants showed antibiotic activity against pathogenic as well as antibiotic-resistant microorganisms, including E . coli , P . aeruginosa and C . albicans . Moreover, in an in vitro C . albicans infection model the tested peptides demonstrated effective amelioration of C . albicans infection without showing cytotoxity on human cells. In summary, protease degradation of hBD-1 provides a yet unknown mechanism to broaden antimicrobial host defense, which could be used to develop defensin-derived therapeutic applications.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-019-40216-2