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

Nature volume 437, pages 975–980 (2005)Cite this article

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.

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Figure 1: Similarity of plectasin to selected invertebrate defensins.
Figure 2: In vitro and in vivo properties of plectasin.
Figure 3: In vivo properties of plectasin.

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Acknowledgements

We thank I. Ellingsgaard, A. L. Hansen, M. Markvardsen, J. Theil, A. Blom, B. Nielsen, B. Cherry, S. Otani and F. Hansen for expert technical assistance.

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Author notes

  1. Olivier Taboureau

    Present address: Novo Nordisk A/S, 2769, Maaloev, Denmark

  2. Per H. Mygind, Rikke L. Fischer and Kirk M. Schnorr: *These authors contributed equally to this work

Authors and Affiliations

  1. Novozymes A/S, 2880, Bagsvaerd, Denmark

    Per H. Mygind, Kirk M. Schnorr, Mogens T. Hansen, Carsten P. Sönksen, Dorotea Raventós, Steen Buskov, Bjarke Christensen, Leonardo De Maria, Olivier Taboureau, Signe G. Elvig-Jørgensen, Marianne V. Sørensen, Bjørn E. Christensen, Søren Kjærulff & Hans-Henrik Kristensen

  2. National Center for Antimicrobials and Infection Control, Statens Serum Institut, 2300 S, Copenhagen, Denmark

    Rikke L. Fischer & Niels Frimodt-Moller

  3. Novo Nordisk A/S, 2880, Bagsvaerd, Denmark

    Svend Ludvigsen

  4. Novozymes Inc., California, 95616, Davis, USA

    Debbie Yaver

  5. Department of Medicine, David Geffen School of Medicine at UCLA, California, 90095, Los Angeles, USA

    Robert I. Lehrer

  6. Departments of Surgery and Pediatrics, Georgetown University Medical Center, DC, 20007, Washington, USA

    Michael Zasloff

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Correspondence to Hans-Henrik Kristensen.

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Competing interests

R.L.F., S.L., N.F.-M., R.I.L. and M.Z. are consultants to Novozymes, and the other authors (P.H.M., K.M.S., M.T.H., C.P.S., D.R., S.B., B.C., L.D.M., O.T., D.Y., S.G.E.-J., M.V.S., B.E.C., S.K. and H.-H.K.) are employees of Novozymes. K.M.S., M.T.H., P.H.M., D.R. Segura and H.-H.K. have filed a patent application that covers this work (ref. 23).

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This file contains Supplementary Figures S1–S5, Supplementary Tables S1 and S2 and Supplemen-tary Methods. (DOC 649 kb)

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Mygind, P., Fischer, R., Schnorr, K. et al. Plectasin is a peptide antibiotic with therapeutic potential from a saprophytic fungus. Nature 437, 975–980 (2005). https://doi.org/10.1038/nature04051

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