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New Findings May Fight Anthrax

By MALCOLM RITTER

..c The Associated Press

Two new findings may someday help doctors deal a one-two punch against

inhaled anthrax, targeting not only anthrax bacteria with drugs like Cipro

but also the poison those bacteria pump out.

It's the toxin that kills, and by the time a person shows symptoms of inhaled

anthrax, antibiotics become less effective because they don't deal with the

toxin already produced by the germs.

The new work, announced Tuesday, may help scientists find ways to neutralize

that toxin. Any new medicines, though, would be years away.

In one study, researchers at the University of Wisconsin-Madison and Harvard

Medical School said they had identified the chemical foothold that anthrax

toxin uses to get inside cells and kill them.

In the other, researchers at The Burnham Institute in La Jolla, Calif.,

Harvard and elsewhere said they have determined the detailed structure of a

protein that does the toxin's dirty work, a discovery that aids in the search

for substances to block it.

The findings, which follow other recent advances toward countering the toxin,

will be published online by the journal Nature on Tuesday and printed in its

Nov. 8 issue.

Anthrax bacteria create three proteins that team up to make its toxin. One,

called protective antigen or PA, latches onto a specific target on the

surface of cells and paves the way for the other two proteins to enter.

Until now, nobody has known what the target was.

That ``has been sort of a holy grail for anthrax research for quite a

while,'' said Duesbery of the Van Andel Research Institute in Grand

Rapids, Mich. Duesbery, an expert on anthrax, wasn't involved in the findings

announced in Nature.

The mystery was solved by Young of the University of Wisconsin-Madison

with colleagues there and at Harvard Medical School. They named the

cell-surface protein they identified ATR for ``anthrax toxin receptor.''

They also found that artificial versions of ATR could keep the toxin from

killing cells in a laboratory dish, by acting as decoys that diverted the

toxin from binding to the cells, Young said.

So treatments with bogus ATR might someday be able to protect people who have

been exposed to anthrax, he said in a telephone interview. However, the idea

hasn't been tested on animals yet.

The work could also aid the search for substances that interfere more

directly with the toxin's attempts to bind ATR, he said.

The other Nature paper reveals the detailed, three-dimensional makeup of

``lethal factor,'' one of the toxin proteins that enters cells. Once it gets

inside immune system cells called macrophages, it destroys them, leading to

shock and often death for victims of inhaled anthrax.

The discovery of lethal factor's structure should enable scientists to design

molecules that can grab onto the protein and disable it, said

Liddington of The Burnham Institute, an author of the paper.

``Maybe a year from now we'd actually have some compounds that would work,''

but they'd still have to go through rigorous testing before they could be

used in people, said Liddington.

Scientists had already been able to protect lab animals from the toxin by

using other proteins that block its effect, although they caution their

efforts are probably years away from useful medicines.

On the Net:

Nature: http://www.nature.com

AP-NY-10-23-01 1401EDT