Fungi on the Defense

Natural Products

A peptide antibiotic discovered in a fungus shows promise as a therapeutic agent, according to a new study. Such antibiotics, known as defensins, have previously been seen in animals and higher plants. The new study is the first to find one in a fungus.

A team led by Hans-Henrik Kristensen, manager of anti-infective discovery at Novozymes in Bagsvaerd, Denmark, discovered plectasin, the new peptide antibiotic, completely by chance while screening the fungus Pseudoplectania nigrella for enzymes of industrial relevance (Nature 2005, 437, 975).

The team tested the therapeutic potential both in culture and in mice. In laboratory tests, plectasin was particularly effective against Streptococcus pneumoniae, including all drug-resistant strains tested. In mice, the peptide was as effective as vancomycin and penicillin against S. pneumoniae.

Plectasin so far seems to have all the properties to become a narrow-spectrum antibiotic, Kristensen says. Of course, many years of preclinical and clinical studies have yet to be carried out. One could anticipate that mutants of plectasin could be identified that have an even broader antimicrobial spectrum while retaining its other positive properties.

Finding a defensin in fungus improves its chances for use as a therapeutic. High production cost is often cited as an obstacle to the development of defensins. In the case of plectasin, however, the producing species can be grown in bulk and provide the peptide antibiotic for relatively low cost, says Robert E. W. Hancock, a professor in the department of microbiology and immunology at the University of British Columbia, Vancouver. Plectasin can be produced with the same system used for the manufacture of industrial enzymes, Kristensen says.