U of A team discovers "Starfish" fights toxins

Thursday, February 10, 2000
Edmonton Journal
Ed Struzik, Journal Staff Writer

EDMONTON - When University of Alberta chemist Pavel Kitov announced he was going to give a talk on the Starfish molecule recently, his research supervisor, David Bundle, had no idea what the Russian postdoctoral fellow was talking about. As it turned out, Starfish was the term Kitov coined to describe the molecule Bundle's team has tailor-made to neutralize the kind of toxins that cause the so-called hamburger disease and cholera, which kills millions each year, and for which there is no cure.

Given the starfish-like structure of the molecule the Alberta team developed, and reports in today's scientific journal Nature, the moniker has stuck in more ways the one.

The scientists now may be on track in developing a treatment for diseases caused by shigella and the closely related cholera toxins.

The University of Alberta has long been a leader in the field of carbohydrate chemistry, the field of research Bundle and his team specializes in.

Retired chemistry professor Ray Lemieux led the world in synthesizing the carbohydrate and sugar molecules which coat the surface of every cell in the body and play a role in many disease processes. Bundle, in fact, holds an endowed chair bearing Lemieux's name. Tailor-making molecules in the war against Shigella and cholera toxins represents another step forward in the battle-plan Lemieux laid out years ago.

The strategy, in Bundle's case, is predicated on a relatively simple disease process. In order for someone to be affected by the

toxic E. coli bacteria, the shiga toxins they produce have to enter the circulatory system. Once in the circulatory system, there is no viable form of therapy, and many victims eventually suffer severe kidney damage.

What Starfish does very effectively, at least in laboratory experiments, is neutralize the shiga-like toxins one to 10 million times more effectively than any previous inhibitor. It does this by attaching itself to the toxins and disarming them of the adhesive properties that allow them to stick to the membranes of healthy human cells for long periods of time.

If the therapy proves to be viable, Bundle envisions that the Starfish might be used as an injectable.

The breakthrough came after four years of research by Bundle's team working in collaboration with a laboratory supervised by microbiology professor Glen Armstrong and x-ray crystallographer Randy Read who is now at the University of Cambridge in Great Britain "The challenge now is to show that Starfish is active against the toxin and harmless to humans," says Bundle. "This involves synthesizing enough of the molecule for tests in models of Shiga toxin poisoning." In light of the lab's breakthrough, the Canadian Bacterial Diseases Network Center of Excellence, which enabled start-up of the research, has committed to six more months of funding for Bundle's lab.

Bundle is decidedly upbeat about the future. The starfish molecule, he believes, shows very promising properties that could shed light on other health threats caused by variant forms of the Shiga toxin which are produced by different strains of bacteria.

Questions and Answers

What are shiga and cholera toxins?

The shiga toxin is produced by a strain of the common E. coli bacterium and causes the so-called hamburger disease, which occasionally breaks out in restaurants and day-care centres. It can be transmitted to humans through improperly cooked meat, unpasteurized milk and impure water.

The closely related toxin responsible for cholera is produced by the bacterium Vibrio cholerae. Approximately one in 20 infected persons has severe disease characterized by profuse watery diarrhea, vomiting and leg cramps. In these people, rapid loss of body fluids leads to dehydration and shock. Without treatment, death can occur within hours. The disease afflicts millions in the Third World.

What is the Starfish molecule?

It's a molecule which at its core has the simple element of glucose. Attached to the glucose are five arms, hence the term Starfish. At the end of each of the arms are the adhesives that bind to the toxins, and prevent them from attaching themselves to a healthy cell.

  Back to News/Media/Events