New antibiotic offers hope for resistance

WASHINGTON, Oct 12, 2005 (UPI via COMTEX) -- Scientists said Wednesday they have discovered a new class of antibiotics in a fungus that is as powerful as penicillin and vancomycin, and it may prove useful in the battle against emerging strains of drug-resistant bacteria.

The antibiotic, called plectasin, showed activity in lab tests against several species of bacteria, including strains of pneumonia-causing Streptococcus pneumoniae that are resistant to currently available antibiotics. Studies in mice indicated plectasin might be safe for use in humans and it protected the animals from bacterial infections that can be deadly.

The discovery opens up the door for identifying many new antibiotics, Dr. Michael Zasloff, co-author of the study and professor in the departments of surgery and pediatrics at Georgetown University Medical Center, told United Press International.

"This discovery will open up an almost inexhaustible supply of antibiotics," Zasloff said. "I do not believe that we will find ourselves in a position in which a microbe will appear for which we will not have an antibiotic to fight it," including strains that are resistant to currently available antibiotics, he added.

The particular fungus this compound was detected in, Pseudoplectania nigrella, was in a sense randomly chosen. Novozymes, a biotech company based in Denmark that led the research, was actually looking for enzymes, not antibiotics.

"So there is no reason not to expect that we will not find many, many more antibiotics of this class as we start to screen the thousands of fungi that are known to exist," Zasloff said.

He said he also expects to find antibiotics that block viruses because fungi use these compounds to protect themselves from pathogens and presumably some must be active against certain viruses present in their environment.

Further work conducted since the discovery of plectasin has already identified other antibiotic compounds in other fungi, Zasloff said. In addition, they have determined that plectasin "works by a different mechanism than any of the known antibiotics," which will make the development of resistance unlikely, he said.

"This finding (plectasin), and the existence of about 200,000 additional species of fungi, opens up a vast universe to explore for novel peptide antibiotics," study co-author Dr. Robert Lehrer, a professor of medicine at UCLA's School of Medicine, said in a statement.

Lehrer said that if plectasin is shown to be safe and effective in further studies in humans, it could be on the market as soon as 2012.

Plectasin has all the characteristics required to turn it into a drug, in terms of cost and the capability to produce it in sufficient amounts, Zasloff said.

The discovery, reported in the Oct. 13 issue of Nature, was made possible by the technique used by Zasloff and colleagues. Instead of traditional techniques, they did a genetic analysis, which enabled them to identify plectasin as a peptide that was similar to other antibiotic compounds called defensins. Traditional techniques for detecting antibiotics failed to turn up any significant amounts in this fungus and thus without the genetic screening, plectasin might have gone undetected, Zasloff said.

Defensins are peptides, or small proteins, that a wide range of plants and animals, including humans, produce to protect themselves from pathogens. Zasloff said researchers have already identified defensins that are active against viruses, such as HIV, but the trick is finding ones that aren't toxic and can be produced as a drug.

In laboratory tests conducted by the Danish National Center for Antimicrobials and Infection Control, plectasin was highly effective against S. pneumoniae and Streptococcus pyogenes -- bacteria that cause meningitis, pneumonia, strep throat, sepsis and flesh-eating infections.

Animal studies also yielded promising results. Plectasin was as effective as another antibiotic, vancomycin, in protecting mice against peritonitis, an infection in the lining of the abdominal cavity. The compound also offered comparable protection to penicillin in defending mice from pneumonia caused by S. pneumoniae.

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