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Wednesday, February 21, 2024

UW, Harvard find key anthrax toxin

UW-Madison researchers announced a breakthrough yesterday in the understanding of anthrax's toxic effect on cells.  




Researchers at the UW-Madison Medical School's McArdle Laboratory for Cancer Research, in collaboration with colleagues at the Harvard Medical School, have identified Anthrax Toxin Receptor, the protein that the anthrax toxin utilizes to gain entry into cells. Authors of the paper describing the discovery, which will be published in the Nov. 8 issue of Nature, include Kenneth Bradley and John Young of UW-Madison, as well as three researchers at Harvard Medical School.  




Antibiotics, specifically Cipro, have been used successfully to prevent infection in individuals exposed to anthrax. However, antibiotics are not very effective once the bacteria cause a full-blown infection. 




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According to Dr. Norman Drinkwater, director of the McArdle Laboratory, the most important aspect of the discovery is that it gives researchers a new way to look for the ability to negate the effects of a full-blown anthrax infection in ways that antibiotics cannot. 




This discovery would be more likely to be used against the inhaled form of anthrax rather than the skin form because anthrax that infects a person through the skin can often be treated before the toxin seriously affects the body. 




'In the inhaled form, the disease has progressed to the point where you have serious effects of the toxin,' Drinkwater said. 




The Wisconsin Alumni Research Foundation has applied for a joint patent with Harvard University for the anthrax discovery, according to Carl Gulbrandsen, executive director of the WARF. 




In the past six weeks, numerous people have been exposed to anthrax, inciting fear across the United States. It has been cited as a cause of three deaths. 




Gulbrandsen said it is too early to tell how useful a patent on this discovery will be, 'until you get to the stage of seeing whether this would work with animals.' 




Secreted by the anthrax bacterium, the anthrax toxin itself consists of three components. Edema Factor and Lethal Factor cause damage once inside the cell; Protective Antigen binds to ATR, facilitating entry of EF and LF. 




'If you do not kill the anthrax bacterium soon after infection, the microbe has time to produce potentially fatal levels of toxin, against which current drugs are not likely to be effective,' said Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases, in a prepared statement. 'These reports greatly increase our understanding of how anthrax toxin destroys cells and offer promising ways to develop treatments for advanced disease by attacking the toxin itself.' 




The researchers were able to force the toxin to stick to newly created ATR outside of the cell, preventing the lethal toxin from getting inside. 




'Now that we know what the anthrax receptor looks like, researchers can screen large numbers of smaller molecules to see if they, too, can prevent the toxin from binding ATR and entering cells,' Young said in a statement.

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