Breaking The Anthrax Code

Anthrax bacteria, microscopic photo AP

The anthrax bacteria first tricks the body's immune cells into attacking it, then quietly kills them before they can call for help, researchers reported Thursday.

The researchers have singled out the mechanism the bacteria uses to do this, opening the possibility of designing an antitoxin to combat it.

Writing in Friday's issue of the journal Science, Michael Karin and Jin Mo Park of the University of California San Diego and colleagues said two potent compounds produced by anthrax, known as "lethal factor" and "protective antigen," team up to deactivate immune system cells called macrophages.

Macrophages are first responders of the immune system, attacking invaders such as bacteria and literally engulfing them. At the same time, they send out chemical signals to call in other immune cells to help.

But anthrax bacteria welcome this embrace, waiting until they are inside the macrophage -- whose name means "big mouth" -- and then sabotaging it.

Karin and Park found it works by inactivating an enzyme called p38 MAP kinase. This causes the macrophage to commit suicide, a process known as apoptosis, before it sends out any signaling chemicals.

The anthrax spore can then take up residence in a lung and pump out its toxins, which cause the often-deadly effects of anthrax infection. When inhaled, anthrax kills up to 90 percent of victims if they do not get antibiotics quickly.

Patients often do not develop symptoms until it is too late. The antibiotics kill the bacteria, but they do not affect the toxins that the bacteria have been producing.

"We've wondered why this bug does not make patients sick early on, especially since it doesn't take many bacteria to make us sick," Karin said in a statement.

"Feeling sick is actually good. It means we're fighting the effects of infection with a fever or runny nose. Not being sick means your immune system is not detecting the infection."

Last year five people were killed and 13 more made seriously ill in a series of anthrax attacks launched by letter. Several did not realize they had anything worse than the flu until it was too late.

Scientists have been working on ways to block the activity of lethal factor and protective antigen. Karin believes it may be easier to do now that the specific target inside the immune cells is known.

"Now we can make predictions that, yes, if you can inhibit that, you can stop macrophages from being killed and give them time to work against infection," Karin said in a telephone interview.

"We have some new insights into the mechanism of pathogenesis -- how to avoid the threat of anthrax as a bioweapon. Somebody needs to make a blocker."

This may fall to the government, added Karin.

"Currently the drug companies certainly don't have a financial incentive to do that. During peace there is no market for such drugs," he said.
  • Sue Chan

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