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Copsin, a novel peptide-based fungal antibiotic interfering with the peptidoglycan synthesis.

  • Essig A From the Institute of Microbiology and.
  • Hofmann D the Institute of Molecular Biology and Biophysics, Swiss Federal Institute of Technology, ETH Zurich, CH-8093 Zurich, Switzerland.
  • Münch D the Institute of Medical Microbiology, Immunology, and Parasitology, Pharmaceutical Microbiology Section, University of Bonn, Bonn 53115, Germany, and.
  • Gayathri S From the Institute of Microbiology and.
  • Künzler M From the Institute of Microbiology and.
  • Kallio PT From the Institute of Microbiology and.
  • Sahl HG the Institute of Medical Microbiology, Immunology, and Parasitology, Pharmaceutical Microbiology Section, University of Bonn, Bonn 53115, Germany, and.
  • Wider G the Institute of Molecular Biology and Biophysics, Swiss Federal Institute of Technology, ETH Zurich, CH-8093 Zurich, Switzerland.
  • Schneider T the Institute of Medical Microbiology, Immunology, and Parasitology, Pharmaceutical Microbiology Section, University of Bonn, Bonn 53115, Germany, and the German Centre for Infection Research (Deutsches Zentrum für Infektionsforschung), partner site Bonn-Cologne, Bonn 53115, Germany.
  • Aebi M From the Institute of Microbiology and markus.aebi@micro.biol.ethz.ch.
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  • 2014-10-25
Published in:
  • The Journal of biological chemistry. - 2014
Antibiotic Resistance
Antibiotics
Antimicrobial Peptide (AMP)
Bacterial-Fungal Interaction (BFI)
Fungal Secretome
Fungi
Lipid II
Agaricales
Amino Acid Sequence
Anti-Bacterial Agents
Bacteria
Coculture Techniques
Defensins
Fungal Proteins
Models, Molecular
Molecular Sequence Data
Peptidoglycan
Protein Conformation
English Fungi and bacteria compete with an arsenal of secreted molecules for their ecological niche. This repertoire represents a rich and inexhaustible source for antibiotics and fungicides. Antimicrobial peptides are an emerging class of fungal defense molecules that are promising candidates for pharmaceutical applications. Based on a co-cultivation system, we studied the interaction of the coprophilous basidiomycete Coprinopsis cinerea with different bacterial species and identified a novel defensin, copsin. The polypeptide was recombinantly produced in Pichia pastoris, and the three-dimensional structure was solved by NMR. The cysteine stabilized α/β-fold with a unique disulfide connectivity, and an N-terminal pyroglutamate rendered copsin extremely stable against high temperatures and protease digestion. Copsin was bactericidal against a diversity of Gram-positive bacteria, including human pathogens such as Enterococcus faecium and Listeria monocytogenes. Characterization of the antibacterial activity revealed that copsin bound specifically to the peptidoglycan precursor lipid II and therefore interfered with the cell wall biosynthesis. In particular, and unlike lantibiotics and other defensins, the third position of the lipid II pentapeptide is essential for effective copsin binding. The unique structural properties of copsin make it a possible scaffold for new antibiotics.
Language
  • English
Open access status
bronze
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Persistent URL
https://folia.unifr.ch/global/documents/217241
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