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03/23/06 News Release

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STANFORD RESEARCHERS FIND NEW APPROACH TO THWART ANTHRAX TOXICITY

STANFORD, Calif. — Most methods of fighting microbial infection focus on killing the microbe, but the bacteria or virus is just one half of the equation. In a paper published in the March 24 issue of Cell, researchers at the Stanford University School of Medicine describe a method of finding human genes that, when inactivated, can also thwart infection. Using this technique, the group found a way to make cells resistant to the deadly anthrax toxin.

Drugs that block proteins made by host genes could provide a new class of antimicrobial drugs, the researchers said. They could also be a much-needed second line of defense in cases where microbes develop resistance to antibiotics or antiviral agents.

“For a pathogen to be harmful it has to enter the cell and replicate, get out of the cell and be in a position to infect more cells,” said Stanley Cohen, MD, professor of genetics and senior author of the paper. “All these steps require host gene products.”

Cohen and research associate Wensheng Wei, PhD, discovered that the LDL receptor-related protein known as LRP6 helps the toxin made by anthrax-producing bacteria enter a cell. “This is a previously unknown function for that protein,” Cohen said.

Wei went on to inactivate the LRP6 protein in cells in a laboratory dish using an antibody. These cells became resistant to the anthrax toxin.

Wei suggested this antibody or drugs that attack LRP6 may protect people from anthrax toxin that remains in their bodies after antibiotics have killed the bacteria themselves. He added that the technique he and Cohen used could also identify genes involved in a wide range of other infections.

Research associate Quan Lu, PhD, also contributed to this work.

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