Scientists learn more about what makes anthrax so deadly

Wednesday, January 23rd 2002, 12:00 am

By: News On 6

Like detectives getting to the whodunit part of a murder mystery, scientists have identified the shape and features of the third protein that allows anthrax to do its deadly work.

While scientists have long known of the existence of the three proteins _ collectively known as anthrax toxins _ only two had been mapped until now. One protein allows the anthrax bacteria to enter cells, while a second destroys immune system cells that normally defend the body.

Now, researchers at the University of Chicago and the Boston Biomedical Research Institute have mapped the 3-D structure of the third protein, called edema factor, which causes swelling and fluid buildup in the body by triggering an adrenaline overload.

The discovery offers another potential target for scientists trying to develop new drug treatments. That, in turn, could speed the development of defenses against bioterrorism.

``When you start talking about what actually goes on in an infected human or animal host, the complexities are just mind-boggling,'' said R. John Collier, a Harvard Medical School researcher who specializes in toxic bacteria. ``It's excellent research that really fills a major void in our understanding of this toxic system.''

Edema factor ``causes an adrenaline increase that mimics the response to outside stimuli, like running away from a fire,'' said Wei-Jen Tang, who led the research at the University of Chicago. ``But in this case, you keep running and running.''

The cells become hyperactive, as if constantly pumped with adrenaline, and devour the chemicals they store for energy. They eventually lose the ability to regulate their environment and die, releasing water that causes swelling _ edema _ in surrounding tissues.

The results can be deadly when anthrax bacteria are inhaled; the protein causes rapid swelling and fluid buildup in the lungs. The less serious form of anthrax, caused when the bacteria infect the skin, results in more limited swelling that is easier to treat.

The findings were published in Thursday's issue of the journal Nature.

More than three months ago, letters tainted with a powerful strain of anthrax were mailed to politicians and media figures in New York and Washington, as well as a supermarket tabloid in Florida. Since then, the Centers for Disease Control and Prevention in Atlanta have confirmed 18 cases of anthrax infection nationwide _ 11 cases of inhalation anthrax and seven through the skin. Five people have died, all from inhaled anthrax.

Tang said researchers also have found that the three anthrax proteins work as a team in the attack. Edema factor, for example, can make the anthrax protein that attacks the body's immune system, called ``lethal factor,'' up to 100 times more potent.

Anthrax ``would be a relatively harmless soil-dwelling bacterium'' if not for the unusual trio of proteins, Robert Liddington of the Burnham Institute in La Jolla, Calif., said in an accompanying commentary.

Liddington said that researchers looking for new anthrax treatments might try developing something that can target edema factor.