Abstract
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.
Highlights
Secreted antibacterial substances of fungi provide a rich source for new antibiotics
Copsin is a novel fungal antimicrobial peptide that binds in a unique manner to the cell wall precursor lipid II
In comparison to a confrontation assay on an agar plate or in a pure liquid culture, this setup has the big advantage of combining a solid surface and a humid environment, two pivotal factors for growth of bacteria and fungi in nature
Summary
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. Significance: Copsin provides a novel highly stabilized scaffold for antibiotics. 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. The unique structural properties of copsin make it a possible scaffold for new antibiotics. One of the best studied types of bacterial-fungal interactions is the antibiosis, where secreted substances play a key role in combating other microorganisms to defend a nutritional niche (1, 2). The chemical shift assignments are available from the BioMagResBank under Number 19880
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