Yeast Protein Prevents Toxic Shock Syndrome

Researchers working with advanced genetic engineering techniques used yeast to create a soluble protein that successfully protected rabbits against the toxic effects of Staphylococcus aureus enterotoxin B (SEB).

Exotoxins of S aureus belong to a family of bacterial proteins that act as superantigens by activating a large subset of the T-cell population, causing massive release of inflammatory cytokines. This cascade can ultimately result in toxic shock syndrome and death.

Investigators at the University of Illinois (Urbana-Champaign, USA) capitalized on a technique they had developed for expressing protein antigens on the surface of yeast cells. The expressed proteins can then be mutated and amplified. In this case, the expressed protein had the same structure as the binding site of the T-cell receptor targeted by SEB. The gene for the binding protein was inserted into Esherichia coli, which produced large quantities of the protein in a soluble form.

Results published in the May 21, 2007, online edition of the journal Nature Medicine revealed that these soluble proteins were effective inhibitors of SEB-mediated T-cell activation and completely neutralized the lethal activity of SEB in animal models.

"We were very pleasantly surprised that it showed effectiveness in every rabbit tested,” said senior author Dr. David M. Kranz, professor of biochemistry at the University of Illinois. "Our approach was to take these receptors that bind to the toxins and to try to make them higher affinity and therefore act as effective neutralizing agents when delivered in soluble form. It is the binding of the toxin to T-cells that is critical. If you can prevent the toxin from binding to the T-cell receptor, then you can prevent it from initiating that cascade.”


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