Twenty years ago no one knew that defensins, a special class of molecules that combat both viruses and bacteria, even existed. They've since been found in nearly every complex organism, yet scientists haven't been able to harness them as disease-fighters. Now, defensins have been discovered in fungi for the first time, a finding that may be key to finally mass-producing these compounds and offering them to patients.
Defensins are short chains of amino acids that poke holes in bacterial membranes, killing the pathogen. They also bind to and disable certain viruses. Nearly every multicellular organism appears to make defensins, with humans alone producing almost 30 different types. But scientists have not been able to mass-produce pure enough concentrations of defensins for drug development and testing, largely because research relies upon fungal-based manufacturing systems developed for penicillin and other antibiotics.
That may change thanks to the discovery of a defensin called plectasin in Pseudoplectania nigrella--a black fungus that grows in European pine forests. The researchers, led by Hans-Henrik Kristensen and Per H. Mygind, both microbiologists at Novozymes, were able to generate large quantities of plectasin by plugging the gene into a fungal protein expression system. To test plectasin's therapeutic benefits, the team gave the compound to mice infected with Streptococcus pneumoniae, the bacterium that causes pneumonia, meningitis, and strep throat. Plectasin was as effective at killing the bugs as penicillin and vancomycin, two commonly prescribed antibiotics. All plectasin-treated mice infected with common strains were cured, and 80% of the mice infected with aggressive strains showed no sign of illness after three days, the researchers report 13 October in Nature.
"There have been several attempts to develop defensins as useful therapeutics, but these attempts have fallen just short of their goal," says Charles Bevins, an immunologist at the University of California, Davis. "This study shows that sufficient plectasin can be generated to allow for a cost-effective means of drug production."