Plectasin is a peptide antibiotic with therapeutic potential from a saprophytic fungus.
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.
Mygind
Per H
PH
Novozymes A/S, 2880 Bagsvaerd, Denmark.
Fischer
Rikke L
RL
Schnorr
Kirk M
KM
Hansen
Mogens T
MT
Sönksen
Carsten P
CP
Ludvigsen
Svend
S
Raventós
Dorotea
D
Buskov
Steen
S
Christensen
Bjarke
B
De Maria
Leonardo
L
Taboureau
Olivier
O
Yaver
Debbie
D
Elvig-Jørgensen
Signe G
SG
Sørensen
Marianne V
MV
Christensen
Bjørn E
BE
Kjaerulff
Søren
S
Frimodt-Moller
Niels
N
Lehrer
Robert I
RI
Zasloff
Michael
M
Kristensen
Hans-Henrik
HH
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
D000900:Anti-Bacterial Agents; D018076:DNA, Complementary; D023082:Defensins; D010455:Peptides; D011994:Recombinant Proteins; C504857:plectasin