Researchers Learn Why
Anthrax Kill - Neutralizing
Protein Sought

From Discovery News Briefs
Researchers are moving closer to finding drugs to disarm anthrax and make the deadly bacteria useless as a weapon.
Anthrax is a rapid and highly effective killer. When it infects, the bacteria produces a toxin, or poison, that attacks cells.
Experts consider anthrax-based biological weapons to be major military threat. Bioterrorism weapons using anthrax or other bacteria are easier to make and distribute than nuclear weapons.
"The only treatment now for anthrax is to give massive, massive amounts of antibiotics," said Nicholas S. Duesbery of the cancer institute. "You have to give it almost immediately after exposure. If you give it 24 hours later, it is too late. Your patient is dead."
"An inhibitor drug would make anthrax as a weapon as useful as a water pistol," said Dr. George F. Vande Woude of the National Cancer Institute and a co-author of the study.
Anthrax toxin consists of three proteins, and early research showed that one of the proteins, called lethal factor, or LF, was the major cause of cell death. But what science didn't know until now is how LF killed the cells.
Vande Woude, Duesbery and their colleagues found that LF disrupts a signaling system in cells called the MAP-Kinase-Kinase (MAP-K-K) pathway. When this system is blocked, said Duesbery, a cell "is cut off from the world." Its metabolism shuts down and it can no longer divide. The toxin also causes the massive release of an inflammation protein and destruction of immune system cells called macrophages.
The result, said Duesbery, is rapid shock and death. In laboratory experiments, he said, "rats are quite dead within just 40 minutes" when injected with anthrax toxin.
Now that researchers know the MAP-K-K target of lethal factor, said Duesbery, "This gives us the first clues of what we need to develop an antitoxin. We can look at the protein structure of the target and come up with (a protein molecule) that will block lethal factor from chopping up its target."
Col. Arthur M. Friedlander, an Army anthrax researcher, said the discovery is significant in understanding how anthrax kills, but he cautioned that it may take more than a single antitoxin to disarm the disease.
"It is not just that toxin that kills in this disease," he said. "But this offers a new approach that may lead to other inhibitors that would work."
Ironically, the anthrax cell target was found while NCI researchers were searching for a way to block the spread of cancer. Vande Woude said the cell-signaling system that the anthrax toxin turns off is permanently turned on in some cancers. The goal now is to use lessons learned from the anthrax research to find a way to selectively shut down the cell signals that promote cancer, he said.
The research is published in the latest journal Science.
Associated Press, Copyright 1998
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