Mutant toxin tested as anthrax antidote

A mutated form of the toxin in the anthrax bacterium could be used to make a fast-acting antidote for people exposed to biological weapons.

Researchers at Harvard Medical School injected laboratory rats with a mixture of mutant toxin and normally lethal amounts of anthrax toxin.

But the rats developed no symptoms of poisoning, says a report on their study in the journal Science.

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

"It's a novel way to interfere with a bacterial infectious process - something entirely new," said lead researcher R. John Collier.

Anthrax is a bacterial disease that generally infects animals such as cattle, sheep and hippopotamuses.

It rarely infects humans, but could be devastating if its spores were used as a biological weapon.

Not surprisingly, the findings have drawn the interest of the US military.

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 cells.

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 Professor Collier said the mutants appeared to block the formation of this channel.

Mutant protective antigen might serve both as an anthrax vaccine and as a fast-acting and broadly protective drug after infection, he said.

The researchers said future studies involving mice would be conducted at US Army laboratories in Maryland.

A vaccine does exist, but very few people outside the military are immunised.

The only way at present to treat anthrax after exposure is with antibiotics before symptoms occur.

"Once an individual becomes symptomatic, it's too late," Professor 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."

Professor Collier said his prime worry was not the use of anthrax in traditional warfare, but as a possible terrorist weapon. He said a Japanese cult had once tried and failed to use anthrax as a weapon, but others might be successful, extremists may try again.

"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."

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

- REUTERS