Forest Fungus Yields Powerful Antimicrobial

Researchers liken its effect to penicillin

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By Amanda Gardner
HealthDay Reporter

WEDNESDAY, Oct. 12, 2005 (HealthDay News) -- A fungus found on the floor of northern European pine forests may soon rescue humans from some of the world's most stubborn diseases.

The mushroom in question has yielded an antimicrobial peptide that researchers say has the curative powers of such antibiotic stalwarts as penicillin and vancomycin, and then some.

In laboratory and animal tests, the peptide, called plectasin, effectively battled a number of bacteria, including strains that have become resistant to conventional antibiotics.

"This particular antimicrobial peptide was extremely active against the organisms that causes pneumonia and the organisms that cause strep throat and certain types of severe skin infections," said Dr. Michael Zasloff, co-author of the study, which appears in the Oct. 13 issue of Nature. Zasloff is professor of surgery at Georgetown University Medical Center in Washington, D.C.

If it passes safety and efficacy tests in humans, plectasin could be on the market by 2012, the study authors stated.

Perhaps more exciting, the findings may usher in a whole new era of antibiotic exploration, discovery and eventual treatment.

"There are hundreds of thousands of fungal organisms," Zasloff said. "We would logically expect, and we anticipate, that as we begin to explore hundreds of thousands of species of fungi, we will most likely uncover antimicrobial peptides that are active against, I would imagine, the entire universe of pathogens that touch man including, very likely, viral organisms."

"This appears to have some systemic activity, meaning you can put it into somebody's body and kill bugs without hurting people, so it does probably represent a major step in this particular field," added Steven Projan, a fellow for the American Academy of Microbiology, and vice president for biological technologies at Wyeth Research in Cambridge, Mass. "It's interesting. It's important. We're a few steps away from using this effectively." Wyeth was not involved with the study.

Antibiotic development has been essentially stagnant since the discovery of penicillin in 1929, said Zasloff, who was the first to discover the existence of antibiotics in the skin of frogs.

"We have been searching for a new class of antibiotics that is produced in the bodies of animals and certain plants for the last 15 to 20 years," he said.

Zasloff was part of an international team of researchers funded by Novozymes, a Danish biotech corporation which had already been exploring fungi for enzymes to use in various commercial drugs.

Fungi were a good place to start looking because the chemicals they make are compatible with human bodies. Indeed, penicillin originally came from fungal "bread mold."

"In the evolution of life in the Darwinian sense, we evolve from fungi. They're between us and plants so basically we're the offspring of fungi," Zasloff explained. "Fungi live on decaying stuff. They sure have to protect themselves and they've got one battle ahead of them as soon as they start to consume decaying material -- and they've got all sorts of tools."

But no "defensins," tiny protein molecules that animals produce to ward off infection, had ever been found in a fungi. The problem lay in the method researchers were using to look for them, Zasloff said.

"The standard techniques for production or discovery of antibiotics have been to grow a penicillin mold in a culture medium and then to take a drop of that culture medium and see if there are antibiotics," Zasloff said. "The antimicrobial peptide is barely produced in that type of scenario. We needed new tools."

The research team used biotechnology to "read" the genetic messages of the Pseudoplectania nigrella species of fungus, which had been picked at random.

Identifying plectasin was only a first step. The second step was to reproduce the peptide in a laboratory.

"We cannot produce an antibiotic unless it can be made, and made commercially," Zasloff explained.

With help from the National Center for Antimicrobials and Infection Control in Denmark, the investigators tested plectasin in the laboratory against a number of different bacteria. While effective against several different organisms, plectasin was particularly active against all clinical strains of S. pneumoniae, the leading cause of pneumonia, including those resistant to conventional antibiotics.

When tested in mice, plectasin proved itself to be safe and effective.

Scientists are hoping not only that plectasin will conduct itself the same way in humans, but that other fungal species will be found to contain peptides to head off other infections, including HIV.

"There's a whole new universe of organisms that we had never really fully explored, and which has yielded for mankind the most effective of our antibiotics," Zasloff said. "It can now be explored."

More information

The Alliance for the Prudent Use of Antibiotics has more on these drugs and the emergence of resistant organisms.

SOURCES: Michael Zasloff, M.D., Ph.D., professor, surgery, Georgetown University Medical Center, Washington, D.C.; Steven Projan, Ph.D. vice president, biological technologies, Wyeth Research, Cambridge, Mass., and fellow, American Academy of Microbiology; Oct. 13, 2005, Nature

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