Proteolytic Degradation of reduced Human Beta Defensin 1 generates a Novel Antibiotic Octapeptide
| Autor: | Bjoern O. Schroeder, Louis Koeninger, Daniela Mailänder-Sánchez, Dirk Ehmann, Martin Schaller, Stephanie Wanner, Jan Wehkamp, Nisar P. Malek, Judith Wendler, Eduard F. Stange, Christopher Weidenmaier, Christina Lemberg, Salomé LeibundGut-Landmann |
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| Přispěvatelé: | University of Zurich, Wehkamp, Jan |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Proteases beta-Defensins medicine.drug_class medicine.medical_treatment Proteolysis Antibiotics Immunology lcsh:Medicine Peptide Article Microbiology 03 medical and health sciences 0302 clinical medicine medicine Humans lcsh:Science chemistry.chemical_classification 1000 Multidisciplinary Protease Multidisciplinary medicine.diagnostic_test Bacteria lcsh:R Fungi Antimicrobial In vitro Corpus albicans Peptide Fragments Anti-Bacterial Agents 030104 developmental biology chemistry Immunologi 570 Life sciences biology lcsh:Q 030217 neurology & neurosurgery 10244 Institute of Virology |
| Zdroj: | Scientific Reports, Vol 9, Iss 1, Pp 1-12 (2019) Scientific Reports |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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