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April 27 , 2001

Scientists Find Novel Way to Subvert Anthrax Germ


By Will Dunham

WASHINGTON (Reuters) - A mutated form of the toxin in the anthrax bacterium could be used to make a fast-acting medicine for people exposed to biological weapons using the deadly germ, as well as a new form of vaccine, scientists said on Thursday.

Harvard Medical School researchers tested whether they could prevent infection using a form of anthrax containing a mutation in a toxin produced by the bacterium.

When the mutant form was injected together with the normally lethal mix of anthrax toxin, laboratory rats did not develop any symptoms of poisoning, according to the study appearing in the journal Science.

Rats infected with the toxin without the mutant variation became moribund within 90 minutes.

``What we've been able to do is to take a component of a toxin and, by making a mutational change in it, you now convert that piece of a toxin into something that will interfere with toxicity,'' lead researcher R. John Collier said in an interview. ``It's a novel way to interfere with a bacterial infectious process -- something entirely new.''

Anthrax is a bacterial disease that generally infects animals such as cattle, sheep and hippopotamuses. It rarely infects humans, but could pose a devastating threat if anthrax spores are used in a biological weapon by terrorists or in warfare. Not surprisingly, the findings have drawn the interest of the U.S. military.

Death is caused by the toxin produced by the bacteria. In its airborne form, a mere teaspoonful of anthrax could wipe out hundreds of people. A big worry is the possible release of anthrax by terrorists in an urban setting.

The Harvard team sought to prevent infection using forms of the anthrax bacterium with a mutation in a toxin component called protective antigen.

The anthrax bacterium secretes three toxin proteins into the bloodstream: protective antigen, lethal factor and edema factor. These assemble into the toxin on the outside surface of human cell membranes. For symptoms to develop, lethal factor and edema factor must move to the cell interior.

Normally, seven protective-antigen molecules form a doughnut-shaped channel that allows the two other proteins to cross the usually impenetrable cell membrane and enter the cytoplasm, where they disrupt cell function. But Collier said the mutants appeared to block the formation of this channel.

A Post-Infection Drug Foreseen

Mutant protective antigen may serve both as an anthrax vaccine and as a fast-acting and broadly protective drug after infection, Collier said. The researchers said future studies involving mice will be conducted at U.S. Army laboratories in Maryland.

A vaccine currently exists, but very few outside the military are immunized. The only current way to treat anthrax after exposure is with antibiotics before symptoms occur.

``Once an individual becomes symptomatic, it's too late,'' Collier said. ``The thing about the inhalational form is that the disease very rapidly progresses from the lungs into the bloodstream, with the result being almost uniformly fatal in a few days.''

Collier said his prime worry is not the use of anthrax in traditional warfare, but as a possible terrorist weapon. He said a Japanese cult once tried and failed to employ anthrax as a weapon, but other extremists may try again.

``The great fear is that this could be used in a terrorist attack on a domestic population,'' Collier said. ``So I think that the domestic authorities could quite possibly be interested, and should be (in the possible future drug). ... This is something that you might want to stockpile in major metropolitan areas around the country and have available.''

Collier said that the approach his team used on anthrax perhaps could be used against other disease-causing bacteria, such as Staphylococcus, that act similarly.

 

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