Two groups of researchers announced today key features of how anthrax toxin destroys cells. In back-to-back papers in the journal Nature, investigators identify how one part of the toxin gets into cells and how another part turns off one of the cell's major internal switches.
The studies also show how at least one molecule can prevent the toxin from destroying cells. Though still in the laboratory stage, these discoveries offer new ways to investigate potential anthrax treatments. The papers appear in a special advance online publication of the journal.
Several types of anthrax exist, but researchers are most concerned with inhalation anthrax, which can occur after a person inhales a large number of bacterial spores. The spores move to the lungs where they germinate, producing a potent toxin. "If you do not kill the anthrax bacterium soon after infection, the microbe has time to produce potentially fatal levels of toxin, against which current drugs are not likely to be effective," says Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), which funded the two studies. "These reports greatly increase our understanding of how anthrax toxin destroys cells and offer promising ways to develop treatments for advanced disease by attacking the toxin itself."
Anthrax toxin has three parts. Two parts, edema factor (EF) and lethal factor (LF), can destroy cells from the inside or prevent them from working. A third component, protective antigen (PA), carries EF and LF into the cells. In the new reports, the researchers asked two critical questions: What molecule on the surface of animal cells does PA use as a doorway, or receptor, for entry; and how does the LF toxin attach to and destroy its intracellular targets.
To answer the first question, the University of Wisconsin's John Young, Ph.D., an expert on receptor molecules, joined forces with John Collier, Ph.D., a Harvard University sp
Contact: Sam Perdue or Laurie K. Doepel
NIH/National Institute of Allergy and Infectious Diseases