Sugar molecule could save millions of lives

Alberta Research
Starfish block toxins that cause cholera, hamburger disease

February 10, 2000
National Post
Brad Evenson

By creating a new sugar molecule in the shape of a starfish, a team of Canadian chemists has found a way to block the toxins that cause cholera, shigellosis and Hamburger Disease, a discovery that could save millions of lives.

"This kind of potential drug…would be injected into those who have severe symptoms", said David Bundle, a professor of chemistry at the University of Alberta.

Each year, up to two million people dies from infection by bacteria that release so-called AB5 toxins. Most victims succumb to severe dehydration caused by diarrhea, while others die from kidney damage and massive internal bleeding.

Cholera and shigella are two common types of bacteria that carry the toxin. But is also found in a particular strain of E. coli commonly found in uncooked meat.

In a report published today in the scientific journal Nature , the Edmonton scientists show a synthetic sugar molecule can prevent AB5 toxins from entering cells and wreaking havoc.

"This toxin is a doughnut-shaped molecule which has to sit down on the membrane of the cell", explains Bundle, lead author of the paper.

"An enzyme which is attached to the toxin the burrows its way through the [cell] membrane and shuts down protein synthesis and the cell dies".

Since the toxin molecule uses sugars on the cell surface to cling to the cell, the scientists wanted to create a fake sugar that would "gum up" its binding sites, much like Scotch tape loses its stickiness when it is covered with dirt.

"When all the sites on the toxin are blocked it can no longer bind to the cell surface", explains Bundle.

The researchers discovered that a five-pronged sugar molecule, dubbed the Starfish, was an ideal candidate for gumming up the toxin. It was designed by Pavel Kitov, a Russian postdoctoral student in Bundle’s lab. The team found that Starfish is one-million-to-10-million times more effective at blocking certain AB5 toxins than any inhibitor yet discovered.

If the Starfish molecule can be turned to medical uses, the implications are enormous.

Shigellosis kills about 600,000 people each year. It is usually not a problem in the developed world, where antibiotics and intravenous fluid replacement are widely available. Its victims are mostly children living in less developed areas with poor sanitary conditions.

In North America, a common strain of E. coli known as 0157:H7 is responsible for hundreds of poisonings each year. While it can be found in unpasteurized apple juice, lettuce and even potato salad, the most common source is undercooked hamburgers. In laboratories, this strain of E. coli is considered as dangerous as anthrax and rabies. Children are the most susceptible to its effects, developing an often fatal kidney condition called Haemolytic Uremic Syndrome.

By turning the Starfish molecule into a drug, it could be used to neutralize the effect of the toxins these bacteria secrete.

There are a few potential medical obstacles, however.

For one thing, the Starfish molecule is very large and heavy. Most medical drugs weigh about 1,000 Daltons, while Starfish is about 8,000 D. Something that big could arouse the body’s immune system to attack it. "I don’t thing it will", said Bundle. "Sugars by themselves are not immunogenic in humans, even complex sugars.

Secondly, the body has many membranes that act as natural filters.

"Will it prevent [Starfish] from reaching the sites that you want to protect, like the kidney, for example, which is where a lot of the damage gets done?" wonders Bundle.

The final problem is more practical. Because of its large weight, it is difficult to synthesize Starfish. The University of Alberta team is struggling to find a cheaper, more efficient methods, but right now, its research funding is due to run out in six months.

  Back to News/Media/Events