Small wonder: taking the bite out of anthrax toxin.Using specially designed submicroscopic submicroscopic /sub·mi·cro·scop·ic/ (-mi?kro-skop´ik) too small to be visible with the light microscope. sub·mi·cro·scop·ic adj. capsules in tests on rats, scientists have neutralized the deadly toxin released by the bacterium that causes anthrax. Although antibiotics can kill the microbe microbe /mi·crobe/ (mi´krob) a microorganism, especially a pathogenic one such as a bacterium, protozoan, or fungus.micro´bialmicro´bic mi·crobe n. , there is currently no means of eliminating the toxin once it's unleashed in a person's body. When Bacillus anthracis Bacillus anthracis Infectious disease A gram-positive organism which causes often fatal infections when its endospores–resistant to heat, drying, UV light, gamma radiation, and many disinfectants–enter the body and cause septicemia Military medicine 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 linch·pin or lynch·pin n. 1. A locking pin inserted in the end of a shaft, as in an axle, to prevent a wheel from slipping off. 2. 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). Ravi S. Kane, a chemical engineer at Rensselaer Polytechnic Institute Rensselaer Polytechnic Institute, at Troy, N.Y.; coeducational; founded and opened 1824 as Rensselaer School; chartered 1826. It was called Rensselaer Institute from 1837 to 1861. in Troy, N.Y., and his colleagues took a novel approach by using liposomes Liposomes Aqueous compartments enclosed by lipid bilayer membranes; liposomes are also known as lipid vesicles. Phospholipid molecules consist of an elongated nonpolar (hydrophobic) structure with a polar (hydrophilic) structure at one end. , 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 liposome (lī`pəsōm', lĭp`ə–), microscopic, fluid-filled pouch whose walls are made of layers of phospholipids identical to the phospholipids that make up cell membranes. 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 The Salk Institute for Biological Studies is an independent, non-profit, scientific research laboratory located in La Jolla, California. It was founded in 1960 by Jonas Salk, M.D., the developer of the polio vaccine. 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 :night have a great deal of value," says Phillip J. Baker, a bacteriologist bacteriologist an expert in the study of bacteria and the diseases they cause. at the National Institute of Allergy and Infectious Diseases in Bethesda, Md. However, he points out that Kane and other researchers have also developed anti-anthrax-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 i antitoxins may hinge on the drugs' prices and ease of storage as well as their effectiveness, Baker says. |
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