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Biologists deploy new kind of `Germ Wars' defense against microbes

WASHINGTON—While the Pentagon struggles to deploy a huge antimissile system against a presumed threat from North Korean rockets, biologists are working to develop tiny "antimicrobial" defenses against harmful germs.

Call it "Germ Wars" instead of "Star Wars."

Researchers are turning an ancient set of natural microbe-killers—first discovered on the skin of frogs—into novel weapons to prevent and treat disease.

The new antimicrobial systems are aimed at bacteria that resist antibiotic medicines, a serious and growing problem. Doctors and hospitals need new tools to fight microbes that overwhelm penicillin, streptomycin and other standard drugs. Infections acquired in hospitals are blamed for 100,000 deaths each year.

The Departments of Defense, Homeland Security and Health and Human Services are also interested in antimicrobial research because they want to find better ways to counter the threat of biological terrorism.

Dr. Samuel Miller, a biochemist at the University of Washington in Seattle, for example, directs a government-supported "Center for Biodefense and Emerging Diseases" that studies ways to strengthen human defenses against the flea-borne bacterium that causes plague, among other diseases.

"Outbreaks of contagious diseases are nothing new," Miller said. "What has changed is the approach to seeking countermeasures to infectious diseases, both those arising naturally and those dispersed intentionally."

The new approach began about 20 years ago, when Dr. Michael Zasloff, a biochemist and now dean of research at the Georgetown University Medical Center in Washington, wondered why frogs, which live in microbe-infested water, never seem to get infected.

The answer, he discovered, was that a frog's skin is covered by a host of short strands of protein that attack and destroy infectious bacteria. Proteins are complex chemical compounds that make up all living tissues.

Since then, scientists have discovered hundreds of these protein snippets—formally called "antimicrobial peptides"—in creatures as varied as amoebas, insects, scorpions, plants and humans. Each species, even each organ of the body, seems to have its own arsenal of peptides suited to its environment.

Antimicrobial peptides found on the skin of crocodiles, for example, allow the big reptiles to thrive among billions of bacteria in the swamps in which they live.

Some primitive tribes in China and Africa use extracts from the skin of frogs to heal wounds, burns and infections, according to Richard Gallo, a dermatologist at the University of California in San Diego. The antiseptic effect of peptides "may explain the beneficial effects of these archaic treatments," said Gallo, editor of a new textbook on antimicrobial peptides.

"By and large we have overlooked the defensive mechanisms that have permitted us to live in harmony with our microbial neighbors," Zasloff said.

Peptides kill bacteria by rupturing their membranes, or outer coat. They serve as "the first line of defense" against disease germs, said Greg Tew, a biochemist at the University of Massachusetts in Amherst.

Unfortunately, antimicrobial defenses, like antimissile defenses, don't always work. In a countermove, some bacteria have developed what amounts to an anti-antimicrobial system—something like the way a hostile nation might put multiple decoys on its ballistic missiles to confuse the defense.

"Bacteria have developed mechanisms to resist killing by antimicrobial peptides," Miller's colleague, Martin Bader, reported in the Aug. 12 issue of the scientific journal Cell. The bacteria sense the presence of a peptide and remodel their membranes in a way that makes them invulnerable to attack.

"The net result is the peptides cannot interact as well with the surface and the bacteria can resist killing," Miller explained in an e-mail message.

Researchers and biotechnology companies are trying to get around the anti-antimicrobial problem by inventing synthetic peptides.

Last January, for example, Tew received a $515,000 grant from the National Science Foundation, a federal agency, to work on artificial systems that mimic natural peptides.

Tew has developed a chemical compound that exploits the antimicrobial activity of silver—a substance whose antiseptic properties were used by the ancient Egyptians. He said his product can be used in medical devices, food equipment, counter tops, even door handles, to reduce the chance of infection.

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To learn more, go to www.horizonpress.com/hsp/books/pep.html and click on the Introduction and Chapter abstracts.

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(c) 2005, Knight Ridder/Tribune Information Services.

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