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Engineered protein effective against Staphylococcus aureus toxin

A research team led by the University of Illinois has developed a treatment for exposure to enterotoxin B, a noxious substance produced by the Staphylococcus aureus bacterium. The team engineered a protein, which was successfully tested in rabbits, that could one day be used to treat humans exposed to the enterotoxin.

S. aureus enterotoxin B (SEB) is a common cause of food poisoning, but if it is inhaled or produced during an infection it can elicit a systemic and sometimes fatal immune response in humans. In purified form, SEB is listed as a potential bioterrorism agent. Other potent S. aureus enterotoxins include the toxic shock syndrome toxin.

These enterotoxins are classed as superantigens because they set off a massive immune response in humans and other animals. They bind to variable regions of T-cell receptors, stimulating a cascade of events, including the systemic release of inflammatory cytokines. In some cases the powerful immune response leads to toxic shock and death.

The research team, led by University of Illinois professor of biochemistry David M. Kranz, included scientists and clinicians from the Boston Biomedical Research Institute and the University of Minnesota Medical School. Their findings appear today in the online edition of Nature Medicine.

The team began by engineering a protein with the same structure as the binding site of the T-cell receptor targeted by SEB. The researchers expressed the engineered protein on the surface of yeast cells (using a process they helped develop, called "yeast display") and generated mutations meant to increase the protein's ability to bind SEB. After several rounds of mutagenesis and screening, graduate student Rebecca A. Buonpane developed a soluble protein with an affinity for SEB that was over a million times that of the original.

"Our approach was to take these receptors that bind to the toxins and to try to make them higher affinity and the
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Contact: Diana Yates
diya@uiuc.edu
217-333-5802
University of Illinois at Urbana-Champaign
21-May-2007


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