By LEE BOWMAN
Scripps Howard News Service
October 12, 2005
Researchers from Georgetown University Medical Center in Washington, the University of California-Los Angeles and the Danish biotech firm Novozymes say the molecule has as much power as penicillin or vancomycin and appears to be highly effective against bacterial strains that have developed resistance against most existing antibiotics.
Specifically, the researchers found a protein called plestacin, the first molecule of its type ever found in fungi. It is part of a class called defensins, miniature protein molecules produced by many animals to protect themselves from infection.
Humans have defensins in white blood cells and in skin, for instance, but it's believed the new fungal defensin is more potent and targets certain bacteria more specifically.
Researchers testing plestacin in lab cultures and in animals found it to be highly effective against the bacteria streptococcus pneumonia and streptococcus pyogenes, including strains resistant to most antibiotics. These bacteria cause such disease as strep throat, meningitis, community-acquired pneumonia, sepsis and flesh-destroying skin infections.
Plestacin could open a whole new front in the war against many common and deadly infections, said Dr. Michael Zasloff, a co-author of the study published in the journal Nature and professor of surgery and pediatrics at Georgetown.
Zasloff said antibiotic development hasn't advanced much since 1929, when Alexander Fleming realized that a fungal bread mold, penicillium, which had landed by chance in a Petri dish in his lab, produced a substance that wiped out staph bacteria.
"Most antibiotics used by humans are produced by fungi and certain soil bacteria," Zasloff said. "Using our existing tools of discovery, we have failed to uncover any new classes of antibiotics from these sources over the past decade. By utilizing a new genetic approach that allowed the team to discover plestacin, we now know that a whole class of antibiotics has been overlooked."
The discovery of plestacin and the existence of about 200,000 other species of fungi "opens up a vast universe to explore" for similar new antibiotic candidates, said Dr. Robert Lehrer, a professor at UCLA's David Geffen School of Medicine and co-author of the study. Plestacin, if proven safe and effective in humans, could be a prescription drug by 2012, he said.
The research was carried out and funded by Novozymes, with Zasloff and Lehrer, both experts in the class of antibiotic proteins that plestacin belongs to, serving as consultants to company researchers.
Scientists have suspected that fungi living in a tough neighborhood - with bacteria and viruses all trying to consume the same rotting matter - must have a strong defense system against microbes. However, attempts to find defensins by culturing fungi have not worked.
The Novozymes team instead used genetic science to search for defensins in fungi and isolate the plestacin protein, then tweaking genetic messages to allow the scientists to produce the protein in large amounts.
Doing further analysis, the researchers found that the antibiotic protein resembles defensins found in spiders, scorpions, dragonflies and mussels, suggesting that they arose from a common ancestral gene and have been around for a about 1 billion years.
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