Antibiotics from a Mushroom

It's just a little black mushroom, but researchers at Georgetown University Medical Center are contending that Pseudoplectania nigrella, found in the woods of northern Europe, may spawn a powerful new class of antibiotics and antivirals.

"I think we are looking at a whole new world of antibiotics," said Michael Zasloff, MD, PhD, of Georgetown University Medical Center. Zasloff and colleagues' discovery was published in the 13 October issue of Nature and reported by MedPage Today on 13 October.
What's Plectasin

"Animals and higher plants express endogenous peptide antibiotics called defensins," write the investigators in their Nature article. "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-Pseudoplectania nigrella."

According to Zasloff, plectasin was tested against a range of bacteria, including streptococcus, enterococcus and staphylococcus, and other defensins have demonstrated anti-viral activity. He added that the existence of about 200,000 other species of fungus make it likely that many more fungal defensins will be found-among which may be highly targeted antimicrobial drugs that will supersede the current generation of broad-spectrum drugs.

"I think we as physicians are going to see assembly of a large number of antimicrobial peptides targeted against specific organisms, including viruses," Zasloff said, according to MedPage Today.

The researchers used a recombinant form of plectasin produced by Danish biotech company, Novozymes, who produced the plectasin at a commercially viable price, yield and purity, Dr. Zasloff reportedly said.
What the Studies Show

In in vitro studies, recombinant plectasin showed high activity against Streptococcus pneumoniae, including strains that are resistant to conventional antibiotics. In animal studies, plectasin showed extremely low toxicity in mice, while curing them of experimental pneumonia and peritonitis caused by S. pneumoniae as effecively as established antibiotics vancomycin and penicillin.

Despite plectasin's apparently low toxicity in mice, Zasloff reportedly said that further studies are necessary to determine if plectasin is safe for humans. However, he believes it is likely that the efficacy seen in mice will also be seen in humans, as the bacterial targets would be identical. Moreover, plectasin is excreted unchanged in mice's urine, which supports its safety and efficacy.
Why a Recombinant?

Plectasin's discovery could not have occurred using conventional techniques, according to Zasloff, in which the fungi would be grown in liquid cultures and tested for antimicrobial activity.

"When this mushroom is grown in the lab, it doesn't produce much plectasin," he reportedly said. Instead, Novozymes researchers went "scouring through the genetic messages" of wild fungi to find genes that code for specific molecules. "One of them coded for what we could clearly see was a defensin."

Now, a walk near his home brings dozens of mushrooms to Zasloff's attention, according to MedPage Today. "It's hard not to go back to the lab and see what they're making."