title: Plectasin is a peptide antibiotic with therapeutic potential from a saprophytic fungus.
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.
authors.affiliation: Novozymes A/S, 2880 Bagsvaerd, Denmark.
authors.forename: Per H
authors.initials: PH
authors.lastname: Mygind
authors.forename: Rikke L
authors.initials: RL
authors.lastname: Fischer
authors.forename: Kirk M
authors.initials: KM
authors.lastname: Schnorr
authors.forename: Mogens T
authors.initials: MT
authors.lastname: Hansen
authors.forename: Carsten P
authors.initials: CP
authors.lastname: Sönksen
authors.forename: Svend
authors.initials: S
authors.lastname: Ludvigsen
authors.forename: Dorotea
authors.initials: D
authors.lastname: Raventós
authors.forename: Steen
authors.initials: S
authors.lastname: Buskov
authors.forename: Bjarke
authors.initials: B
authors.lastname: Christensen
authors.forename: Leonardo
authors.initials: L
authors.lastname: De Maria
authors.forename: Olivier
authors.initials: O
authors.lastname: Taboureau
authors.forename: Debbie
authors.initials: D
authors.lastname: Yaver
authors.forename: Signe G
authors.initials: SG
authors.lastname: Elvig-Jørgensen
authors.forename: Marianne V
authors.initials: MV
authors.lastname: Sørensen
authors.forename: Bjørn E
authors.initials: BE
authors.lastname: Christensen
authors.forename: Søren
authors.initials: S
authors.lastname: Kjaerulff
authors.forename: Niels
authors.initials: N
authors.lastname: Frimodt-Moller
authors.forename: Robert I
authors.initials: RI
authors.lastname: Lehrer
authors.forename: Michael
authors.initials: M
authors.lastname: Zasloff
authors.forename: Hans-Henrik
authors.initials: HH
authors.lastname: Kristensen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D023082:Defensins / Q000737:chemistry; D004195:Disease Models, Animal; D005658:Fungi / Q000737:chemistry* / Q000235:genetics; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000502:physiology; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides; D011008:Pneumococcal Infections / Q000188:drug therapy / Q000382:microbiology; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D018076:DNA, Complementary; D023082:Defensins; D010455:Peptides; D011994:Recombinant Proteins; C504857:plectasin