Since the recent emergence of anthrax as a bioterrorist weapon, researchers have scrambled to learn more about the bacterium's deadly toxin and ways to disarm it. Now, researchers at the University of Padova in Italy and the Pasteur Institute in Paris have developed a test to screen for substances that inhibit lethal factor (LF)—an enzyme that is a key component of the toxin—and have created compounds that block LF's effects in cells.
After LF gains entry into macrophages and other cells, it specifically cleaves certain proteins involved in normal cell signaling and blocks signals that would normally summon other immune cells to fight the infection. The researchers created synthetic substrates for LF that are capable of detecting the activity of minute amounts of the enzyme. With these substrates in hand, scientists can quickly screen vast numbers of chemicals for their ability to inhibit LF's toxic effects.
The investigators also modified their LF substrates to create compounds capable of entering host cells, binding to LF, and blocking the enzyme's toxic effects. The work should help "answer the urgent call for new and specific therapies to combat this pathogen after its recent emergence as a terrorist bioweapon," the researchers said.
The group's findings were published in the July 25 issue of Nature.
