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The skin of frogs may have secret for fighting microbes

SUNDAY, SEPT. 11, 2005

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, 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.

Peptides kill bacteria by rupturing their membranes, or outer coat.

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.


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