Copsin, a Novel Peptide-based Fungal Antibiotic Interfering with the Peptidoglycan Synthesis

Abstract

Background: Secreted antibacterial substances of fungi provide a rich source for new antibiotics. Results: Copsin is a novel fungal antimicrobial peptide that binds in a unique manner to the cell wall precursor lipid II. Conclusion: As part of the defense strategy of a mushroom, copsin kills bacteria by inhibiting the cell wall synthesis. Significance: Copsin provides a novel highly stabilized scaffold for antibiotics.

Intracellular Targeting Mechanisms by Antimicrobial Peptides

“…It is able to bind to the precursor lipid II, particularly at the third position of the pentapeptide, leading to inhibition of cell wall biosynthesis (144). In addition, the fungal AMP plectasin produced by the saprophytic ascomycete Pseudoplectania nigrella effectively inhibits lipid II for its intracellular activity (145).…”

“…Copsin is extremely resistant to proteolysis and wide range of pH and temperature due to the presence of the unusually high number of (six) disulfide bonds, compared to only three or four in other cysteine-stabilized alpha/beta (CS␣␤) defensins (144). It is able to bind to the precursor lipid II, particularly at the third position of the pentapeptide, leading to inhibition of cell wall biosynthesis (144).…”

Fungal proteinaceous compounds with multiple biological activities

“…Different from other defensins and lantibiotics, the third position of the lipid II pentapeptide is of paramount importance to binding of copsin. Copsin is a candidate as a new antibiotic (Essig et al 2014).…”

When green and red mycology meet: Impressions from an interdisciplinary forum on virulence mechanisms of phyto- and human-pathogenic fungi

“…Di Pietro (S) 31,32 Fungal spore components determine the interaction with immune cells A. Brakhage (S) 38 Regulatory networks of C. albicans morphogenesis are complex C. D'Enfert (S) 41 Experimental evolution reveals unexpected factors of fungal virulence S. Brunke (Y) 75,76 Candida albicans produces a toxic surprise: Candidalysin J. Naglik (S) 56 Coprinopsis cinerea produces potent fungal defense effectors M. K€ unzler (S) [59][60][61] The fungal cell wall acts as immunological & drug target N. Gow (S) 70 Copper detoxification supports A. fumigatus virulence N. Osherov (Po) 77 Note. a P: plenary lecture, S: session talk, Y: young researcher presentation, Po: poster plant pathogenic fungi and might reveal natural products that are active in either host, be it plant or human.…”

“…57,58 The session was closed by Markus K€ unzler from the ETH Z€ urich in Switzerland, who impressively demonstrated the systemic intracellular defense response of Coprinopsis cinerea after fungivorous nematode attack to produce nematotoxic lectins and the secretion of extracellular effectors presumably acting against bacterial competitors. [59][60][61] The basic unit of virulence -cell biology of infection (Session 6)…”