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

Per H. Mygind, Rikke L. Fischer, Kirk M. Schnorr, Mogens T. Hansen, Carsten P. Sönksen, Svend Ludvigsen, Dorotea Raventós, Steen Buskov, Bjarke Christensen, Leonardo De Maria, Olivier Taboureau, Debbie Yaver, Signe G. Elvig-Jørgensen, Marianne V. Sørensen, Bjørn E. Christensen, Søren Kjærulff, Niels Frimodt-Moller, Robert I. Lehrer, Michael Zasloff and Hans-Henrik Kristensen ()
Additional contact information
Per H. Mygind: Novozymes A/S
Rikke L. Fischer: Statens Serum Institut
Kirk M. Schnorr: Novozymes A/S
Mogens T. Hansen: Novozymes A/S
Carsten P. Sönksen: Novozymes A/S
Svend Ludvigsen: Novo Nordisk A/S
Dorotea Raventós: Novozymes A/S
Steen Buskov: Novozymes A/S
Bjarke Christensen: Novozymes A/S
Leonardo De Maria: Novozymes A/S
Olivier Taboureau: Novozymes A/S
Debbie Yaver: Novozymes Inc.
Signe G. Elvig-Jørgensen: Novozymes A/S
Marianne V. Sørensen: Novozymes A/S
Bjørn E. Christensen: Novozymes A/S
Søren Kjærulff: Novozymes A/S
Niels Frimodt-Moller: Statens Serum Institut
Robert I. Lehrer: David Geffen School of Medicine at UCLA
Michael Zasloff: Georgetown University Medical Center
Hans-Henrik Kristensen: Novozymes A/S

Nature, 2005, vol. 437, issue 7061, 975-980

Abstract: Abstract 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.

Date: 2005
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DOI: 10.1038/nature04051

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