Plectasin is a peptide antibiotic with therapeutic potential from a saprophytic fungus : Nature

Nature 437, 975-980 (13 October 2005) | doi: 10.1038/nature04051

Plectasin is a peptide antibiotic with therapeutic potential from a saprophytic fungus

Per H. Mygind^1,⁸, Rikke L. Fischer^2,⁸, Kirk M. Schnorr^1,⁸, Mogens T. Hansen¹, Carsten P. Sönksen¹, Svend Ludvigsen³, Dorotea Raventós¹, Steen Buskov¹, Bjarke Christensen¹, Leonardo De Maria¹, Olivier Taboureau^1,⁷, Debbie Yaver⁴, Signe G. Elvig-Jørgensen¹, Marianne V. Sørensen¹, Bjørn E. Christensen¹, Søren Kjærulff¹, Niels Frimodt-Moller², Robert I. Lehrer⁵, Michael Zasloff⁶ and Hans-Henrik Kristensen¹

Animals and higher plants express endogenous peptide antibiotics called defensins. These small cysteine-rich peptides are active against bacteria, fungi and viruses. Here we describe plectasin—the first defensin to be isolated from a fungus, the saprophytic ascomycete Pseudoplectania nigrella. Plectasin has primary, secondary and tertiary structures that closely resemble those of defensins found in spiders, scorpions, dragonflies and mussels. Recombinant plectasin was produced at a very high, and commercially viable, yield and purity. In vitro, the recombinant peptide was especially active against Streptococcus pneumoniae, including strains resistant to conventional antibiotics. Plectasin showed extremely low toxicity in mice, and cured them of experimental peritonitis and pneumonia caused by S. pneumoniae as efficaciously as vancomycin and penicillin. These findings identify fungi as a novel source of antimicrobial defensins, and show the therapeutic potential of plectasin. They also suggest that the defensins of insects, molluscs and fungi arose from a common ancestral gene.

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Novozymes A/S, 2880 Bagsvaerd, Denmark
National Center for Antimicrobials and Infection Control, Statens Serum Institut, 2300 Copenhagen S, Denmark
Novo Nordisk A/S, 2880 Bagsvaerd, Denmark
Novozymes Inc., Davis, California 95616, USA
Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA
Departments of Surgery and Pediatrics, Georgetown University Medical Center, Washington DC 20007, USA
†Present address: Novo Nordisk A/S, 2769 Maaloev, Denmark
*These authors contributed equally to this work

Correspondence to: Hans-Henrik Kristensen¹ Correspondence and requests for materials should be addressed to H.-H.K. (Email: hahk@novozymes.com). Plectasin DNA sequence has been submitted to EMBL with the accession numbers EMBL:AJ964941 and TREMBL:CAI83768. Plectasin coordinates have been deposited to the Protein Data Bank under accession number 1ZFU, and relevant NMR data will be submitted to the Biological Magnetic Resonance Data Bank.

Received 24 February 2005; Accepted 20 July 2005

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