Fungi could harbour most powerful antibiotic source

     Washington: A team from Denmark-based biotech company Novozymes, researchers from Georgetown University Medical Center and the David Geffen School of Medicine at UCLA have found a new class of antibiotics which is effective against drug- resistant bacteria in fungi. According to a study published in the recent issue of Nature, a peptide identified in a fungus found in northern European pine forests possesses as much power as penicillin as well as vancomycin. The researchers say they have isolated 'plectasin', the first defensin ever found in fungi. Defensins are peptides, miniature protein molecules that are produced by a wide range of animals to protect themselves against infection. Humans have defensins in their white blood cells and in their skin, for example, but it is believed that this new fungal defensin, plectasin, is more potent and targets certain bacteria more specifically. Indeed, when plectasin was tested in the laboratory and in animals, it proved to be highly effective against some bacteria, including strains that are now resistant to conventional antibiotics.

     These bacteria are responsible for such diseases as meningitis, community-acquired pneumonia, strep throat, life- threatening sepsis, and flesh destroying skin infections. The discovery of plectasin has implications for the development of defensins as a treatment against many common, and deadly, infections, and may initiate a new era of antibiotic discovery and development, said study co-author Michael Zasloff. "Most antibiotics used by humans are produced by fungi and certain soil bacteria. Using our existing tools of discovery, we have failed to uncover any new classes of antibiotics from these sources over the past decade. However, by utilizing a new genetic approach that allowed the team to discover plectasin, we now know that a whole class of antibiotics has been overlooked," Zasloff 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," said co-author Robert Lehrer. The research team instead used the latest genetic science to search for the defensins they thought fungi must have. "I started working on antimicrobial peptides over three decades ago, said Lehrer, and my laboratory first described human defensins in 1985. So, the discovery of plectasin makes me feel like a grandfather," said Lehrer. Further examination revealed that this defensin, plectasin, resembles defensins found in spiders, scorpions, dragonflies and mussels - thus suggesting that the defensins found in insects, molluscs and fungi arose from a common ancestral gene, the researchers say.

    Based on this information, the scientists now believe that defensins appeared in living things more than a billion years ago. The investigators then turned to the National Center for Antimicrobials and Infection Control, the Danish equivalent of the U.S. Centers for Disease Control, to test plectasin in the laboratory for antimicrobial activity against a broad spectrum of bacteria. It showed potent activity against several species of Gram- positive bacteria, and was especially active against S. pneumoniae (the leading cause of pneumonia), including all known clinical strains and those that are now resistant to conventional antibiotics. "As a group, defensins exhibit activity against many types of bacteria, fungi, protozoa, and even viruses. It is entirely possible that fungal defensins will be discovered that could be developed against all of these human pathogens," Zasloff added.
Oct 13, 2005

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