Researchers at Harvard Medical School and the University of Wisconsin Medical School have found the docking protein, or receptor, for anthrax toxin. The long-sought protein is thought to be the first point of contact between the toxin and the cell it will eventually destroy.
The discovery, reported in Nature online on Oct. 23, and in the Nov. 8 print issue, is expected to lead to a clearer understanding of how the anthrax toxin enters the cell where it works its destruction and, perhaps, to a strategy for fighting infection in people even after symptoms develop.
The scientists have also engineered a fragment of the anthrax toxin receptor (ATR) protein. When added to cells growing in a petri dish, the ATR fragment blocks toxin binding to the cell surface, a finding that may have important repercussions for treatment, since by blocking the binding, the fragment interrupts the fatal sequence of events whereby the toxin does its killing.
An effective antidote to toxin is crucial because once the flulike symptoms of inhalation anthrax become apparent, it is generally too late for medical intervention. This is because antibiotic-insensitive toxin is already circulating and once in the cell, causing irreparable damage.
“Our short-term goals are to study the mechanism of toxin uptake through ATR and to make enough of the toxin-blocking form of the receptor so that it can be tested in animal systems,” said senior author John A. T. Young, the Howard M. Temin professor of cancer research at Wisconsin.
This is the third time in six months that scientists working with R. John Collier, the study’s co-author and the Maude and Lillian Presley professor of microbiology and molecular genetics at the Medical School, have devised a strategy to block toxin action. The researchers hope that some or all of the methods may eventually lead to an antidote against anthrax infection.