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Scientists design potent anthrax toxin inhibitor

Scientists funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), have engineered a powerful inhibitor of anthrax toxin that worked well in small-scale animal tests.

"This novel approach to the design of anthrax antitoxin is an important advance, not only for the value it may have in anthrax treatment, but also because this technique could be used to design better therapies for cholera and other diseases," says NIH Director Elias A. Zerhouni, M.D.

The research appears in the April 23 online edition of the journal Nature Biotechnology.

Led by NIAID grantees Ravi S. Kane, Ph.D., of Rensselaer Polytechnic Institute, in Troy, NY, and Jeremy Mogridge, Ph.D., of the University of Toronto, the investigators built a fatty bubble studded with small proteins that can cling tightly to the cell membrane receptor-binding protein used by anthrax toxin to gain entry into a host cell.

The protein-spiked fatty bubble, or "functionalized liposome," hampers a critical early step in the assembly process that anthrax toxin must undergo to become fully active. In test-tube experiments, the inhibitor, which is covered with multiple short proteins (peptides), was 10,000 times more potent than unattached peptides.

"If the effectiveness of anthrax inhibitors designed in this fashion is confirmed by additional testing, they could one day be important adjuncts to standard antibiotic therapy for the treatment of inhalation anthrax," says NIAID Director Anthony S. Fauci, M.D.

The spore-forming bacterium Bacillus anthracis produces a toxin that causes anthrax symptoms. Antibiotics are used to treat anthrax, but even with such therapy, inhalation anthrax, the most severe form of the disease, has a fatality rate of 75 percent.

"There would be real value to having an additional form of therapy available to physicians confronting a case of inhalation anthrax," notes Phillip
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Source:NIH/National Institute of Allergy and Infectious Diseases


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