anthrax

After the bioterrorism events of last fall, researchers are more anxious than ever to find drugs to combat anthrax. To that end, findings described today in the journal Nature should prove useful. According to the report, scientists have determined the structure of the last of three poisonous proteins that make up anthrax's deadly toxin.

Earlier work had revealed the makeup of the other two triad components. The first of these, known as protective antigen (PA), facilitates entry of the other two into target cells; the second, lethal factor, destroys immune cells. But the third component, dubbed edema factor (EF) for the fluid accumulation it causes, may be the most insidious of the three. Wei-Jen Tang of the University of Chicago and colleagues discovered that EF disables a signaling molecule in the host cell called calmodulin and then uses it to power its own activity. Ultimately, this molecular hijacking squelches the immune response to the anthrax bacterium (see image), allowing it to spread.

Yet as dangerous as it is, EF may also represent the anthrax toxin's Achilles' heel. Analysis of its 3D structure has revealed that EF's active site is a deep pocket that could serve as a target for future drugs. "Three years ago, when we started this project, Bacillus anthracis was an obscure agricultural pathogen with interesting biological properties," Tang reflects. "Now anthrax is front and center in every clinician's mind, and within months of the first bioterrorism case we have the structures for all three toxins. We hope this work will quickly lead to new therapies."