BBC

Progress in fight against anthrax

A way to defeat anthrax is one step closer, thanks to two new scientific advances.

A US team has pinpointed how anthrax toxins invade the cells of the human body, raising hopes of finding new means to combat the deadly bug.

In a separate development, international researchers have identified the 3-D structure of one of the anthrax toxins.

The knowledge could lead to new drugs for anthrax which, in its most dangerous inhaled form, is almost always fatal.

Anthrax, a disease caused by spores of the bacterium Bacillus anthracis, can be treated with antibiotics.

But if the spores are inhaled and enter the lungs they may stay hidden for weeks or months, progressing to a stage that is very difficult to treat.

Achilles heel

Now a US team, from the University of Wisconsin-Madison and Harvard Medical School, has identified a possible "Achilles heel" of the bug - they have found out how the toxins that poison the body enter human cells.

They bind to human cells using a docking structure that is made of a single protein called anthrax toxin receptor (ATR).

The scientists have genetically engineered a form of ATR that they have used to block the anthrax toxin from entering cells.

Lead researcher Dr John Young said: "Our short-term goals are to study the mechanism of toxin uptake through ATR and to make enough of the toxin-blocking form of the receptor so that it can be tested in animal systems.

"A more long-term application would be for pharmaceutical companies to use the receptor along with anthrax toxin to screen the millions of compounds they've already synthesized to identify toxin inhibitors."

Toxin

Once it enters its host, the anthrax bacterium secretes a toxin consisting of three components.

Two of them - edema factor (EF) and lethal factor (LF) - wreak havoc inside cells.

The third component, protective antigen (PA), binds to ATR and acts like a doorway for EF and LF to enter the cell.

In separate research, a team from the Burnham Institute in California has worked out the 3-D structure of LF.

Lead researcher Dr Robert Liddington said: "We knew from earlier biochemical studies that LF was the key player in death from anthrax, so determining its 3-D structure could tell us a lot about how it works and thus how to disarm it."

LF works by entering the cell and severing the communication pathway the cell uses to alert the immune system to infection.

The 3-D structure reveals how LF binds to a particular protein to block the alarm signals.

Dr Liddington said: "The structure tells us how LF recognises just one protein among thousands, and thus how we could design drugs to block that recognition."

Important tool

Dr Andrew Pannifer, who contributed to the research, told BBC News Online: "This work is likely to be an important tool in the development of medications to block anthrax toxin but is not in itself a cure.

"Understanding the structure of the toxin and getting a better appreciation of how it works will guide the development of molecules which are able to bind to it, inhibit it and block its effects."

The current antibiotic used to treat anthrax, ciprofloxacin, kills the bacteria produced by anthrax infection, but does not block the toxin.

By the time symptoms have appeared, so much toxin has already accumulated that it has reached fatal levels.

-- Anonymous, October 25, 2001