Recent anthrax fatalities have underscored that if patients with inhalation anthrax are not treated with appropriate antibiotics soon after infection, anthrax bacteria have time to churn out lethal quantities of a potent cell-killing toxin. Now, scientists in England and the United States have discovered how one component of anthrax toxin targets a critical protein in human cells—a finding they believe lays the groundwork for new treatments for the illness.
Researchers at the University of Leicester in England, the Burnham Institute, in La Jolla, Calif, and other institutions used X-ray crystallography to study how lethal factor (LF), one of three components of anthrax toxin, binds to the cellular protein it targets. When LF enters and kills macrophages (the cell type most affected by anthrax toxin), the cells release high levels of inflammatory molecules, plunging the system into shock.
The X-ray studies yielded a detailed look at the LF's surface and revealed how a groove in LF precisely fits the target molecule. "This information can be used in the design of therapeutic agents that would block the activity of LF in vivo," the researchers said.
The new findings were published in the November 7 issue of Nature. In a second paper in the same issue, researchers in the United States reported they had discovered the cell surface receptor used by anthrax toxin to gain entry into target cells. Both papers are also available online at http://www.nature.com/nature/anthrax.
