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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, to review whether dissemination plays a role in the successful uptake of new Three Rs methods. The main conclusions from the workshop are summarised in this report. There is probably sufficient awareness about the need for the Three Rs, due to societal and legislative pressure and industry requirements. Also, there are many opportunities for gaining funding for research, and an abundance of organisations to provide information on the Three Rs, although these tend to work in isolation. The EPAA workshop identified a gap. This was the absence of a process and/or organisation/institution supporting the postvalidation and implementation of new methods that would help ensure the rapid and widespread uptake of new alternative methods. The case studies presented at the workshop have clearly illustrated that what has been achieved so far is mainly due to the resource and perseverance of personal champions. This is not a very efficient way forward for the future. Since dissemination plays an important role during the post-validation/implementation phase and for regulatory acceptance, the EPAA will see whether the synergy between the dissemination and validation and acceptance work strands can be improved, and will ensure that the regulatory authorities are consulted.