How anthrax gets a grip on cells

Scientists have identified the key structures of the anthrax bacterium that could lead to antitoxins and other treatments for the infection.

The research, some of it begun as long as five years ago, is fortuitously bearing fruit just as the disease is the focus of a biological terrorism scare in the United States. Any medicines arising from the work, however, will not appear for a year or two at the earliest, experts have said.

The National Institutes and the United States army are among the organisations starting to search for drugs based on the new studies, which will appear in the journal Nature this month but were released on the journal's website on 23 October (http://www.nature.com/nature/anthrax/).

The anthrax toxin is composed of several distinct molecules. Before the toxin enters a cell, its parts—“oedema” factor, “lethal” factor, and seven copies of “protective” factor—bind together as a unit. They then attach to a protein receptor that is found on the surface of human cells and continue to release oedema factor and lethal factor into the cell.

The release of these toxins triggers illness and, ultimately, death. Few people survive when the microbe becomes widespread in the body, as happens in the severe, inhalational form of the disease and occasionally in skin anthrax infections. This is because the toxin remains active in the bloodstream for several days, even if antibiotics kill the bacteria that are producing it.

The new research illuminates how the toxin gets into healthy cells and how it disrupts the cell's internal communications network once it arrives. In one study Dr John Young of the University of Wisconsin and his colleagues identified the receptor for the toxin complex. They began by creating genetic mutations in hamster cells, hoping that at least one cell by chance would lose the receptor and become impervious to anthrax toxin. They found 10 cells and chose one to investigate, from which they were able to identify the DNA sequence of the gene for the receptor.

In the other study Dr Robert Liddington of the Burnham Institute, an independent non-profit making research organisation in La Jolla, California, determined the three dimensional structure of the lethal factor. It has a groove that “recognises” and then destroys an important enzyme in immune system cells, crippling them.