Small Wonder: Taking the bite out of anthrax toxin

Using specially designed submicroscopic capsules in tests on rats, scientists have neutralized the deadly toxin released by the bacterium that causes anthrax. Although antibiotics can kill the microbe, there is currently no means of eliminating the toxin once it’s unleashed in a person’s body.

When Bacillus anthracis infects a mammal, it secretes three proteins that together prove lethal. One of the proteins, called protective antigen (PA), acts as the scout, latching on to a cell. That bond enables the other two anthrax-toxin proteins to enter the cell and kill it.

Because it’s the linchpin for cell invasion, PA is an obvious target for antianthrax drugs. Some synthetic compounds had shown promise in binding to PA and blocking the toxin’s lethal effect (SN: 10/6/01, p. 212: Chemical Neutralizes Anthrax Toxin).

Ravi S. Kane, a chemical engineer at Rensselaer Polytechnic Institute in Troy, N.Y., and his colleagues took a novel approach by using liposomes, small vesicles that have a membrane of fat molecules. Liposomes have already been approved to deliver drugs to cells in other diseases.

Kane’s team studded the surface of each liposome with peptides that can attach to the sites on the PA protein that bind to a cell. The researchers spaced the peptides to match the array of binding sites on PA. That increased the likelihood that the liposome would tightly bind PA, which then wouldn’t be available to attach to a cell, Kane says.

The scientists injected two different doses of the liposomes into two groups of nine rats, each of which had just been injected with anthrax toxin. In the group that got the higher dose, only one rat became gravely ill. In the group that received the lower dose, four animals became seriously ill. A third group of nine rats received only anthrax toxin. Eight of those animals became severely ill, the researchers report in an upcoming Nature Biotechnology.

Kane plans next to test the liposomes on animals that already have an established anthrax infection.

The findings suggest that the liposomes might serve as an anthrax-drug candidate, says John A.T. Young, a microbiologist at the Salk Institute for Biological Studies in La Jolla, Calif. “Clearly, this is a viable approach,” he says.

The liposome researchers have made rapid progress in only a few years and “have identified a product that might have a great deal of value,” says Phillip J. Baker, a bacteriologist at the National Institute of Allergy and Infectious Diseases in Bethesda, Md. However, he points out that Kane and other researchers have also developed antianthrax-toxin agents that use polymers as a scaffolding for peptides that bind PA. It remains unclear whether liposomes are markedly more efficient than the polymers are, Baker says, although liposomes may have an advantage in gaining regulatory approval.

The final choice for stockpiling anthrax antitoxins may hinge on the drugs’ prices and ease of storage as well as their effectiveness, Baker says.