Potential Anthrax Antidote Shows Promise in Rats

By Amy Norton

Reuters Health

April 26, 2001

NEW YORK (Reuters Health) - In a discovery that could lead to new and better treatments for deadly anthrax infections, scientists have found a way to turn one of the bacterium's key infectious components against it.

Although anthrax rarely infects humans, health officials consider the toxin a threat because of its potential use as a biological weapon. Antibiotics can treat the infection, but they must be given quickly--a fact that has investigators hunting for treatments that can be given later in the course of the illness.

In the April 27th issue of Science, researchers at Harvard Medical School in Boston, Massachusetts, report on their initial success in making part of the anthrax toxin work against itself. In experiments with rats, Dr. John Collier and his colleagues were able to protect the animals from anthrax toxin by treating them with a mutant form of an anthrax protein.

The protein, called protective antigen (PA), is one of three that make up anthrax toxin. These three proteins work together to allow the bacteria to invade and destroy healthy cells. The role of PA molecules is to get the other two proteins into people's cells to do their dirty work. They accomplish this by forming a ``doughnut'' shape that safely ushers the other two proteins past the body cells' defense mechanisms.

But Collier and his colleagues found that if they replaced one of the PA molecules with a mutant form, this effectively took a bite out of the doughnut and prevented the anthrax toxins from getting into the healthy cells of rats.

Anthrax infection is caused by a spore-forming bacterium. While it usually occurs in plant-eating animals like cattle, sheep and goats, it can be spread to humans when they handle or eat contaminated animal products. Humans can also contract anthrax by inhaling bacterial spores, making the bacteria a potential weapon of biological warfare.

Collier told Reuters Health that his team will next study whether their mutant PA can protect animals exposed to anthrax spores, which will give it more of a real-world test. In this study, the rats were exposed only to the three anthrax proteins.

And, Collier noted, it is still unknown whether the mutant PA could be used to treat animals--and humans--after they have developed anthrax symptoms. This is a key question because antibiotics must be given within a day or so of anthrax exposure. Once symptoms have developed, Collier said, it is too late. Anthrax contracted through inhalation is usually fatal.

Along with the time factor, the growing problem of antibiotic resistance is another reason an alternative anthrax treatment is needed, according to an editorial accompanying the report.

``It is therefore important to be able to treat bacterial infections as soon as they occur with therapeutics other than antibiotics,'' write Sjur Olsnes and Jorgen Wesche of the Norwegian Radium Hospital in Oslo.

They call this study ``an innovative example of how this can be achieved.''

SOURCE:

http://dailynews.yahoo.com/h/nm/20010426/hl/anthrax_1.html

Science 2001;292:695-697.