Case Number 107093 - Novel Molecules for Shiga Toxin Detection
Contact: Jill Uhl
Description: Shiga toxin producing Escherichia coli (STEC), including E. coli O157:H7, are emerging pathogens of major importance. E. coli O157:H7 alone causes an estimated 70,000 cases of disease per year in the United States. Disease caused by E. coli O157:H7 is characterized by diarrhea, hemorrhagic colitis, and the potentially fatal complication, hemolytic uremic syndrome (HUS). Shiga toxin (Stx) is a major virulence factor of E. coli O157:H7 and has been included as a Select Agent of Biothreat agent list.
The pathogenic potential of an E. coli isolate is dependent on the type of Shiga toxin it produces. There is an urgent need for diagnostic agents that can discriminate between Stx1 and the deadlier form, Stx2, for effective intervention and the prevention of future outbreaks. Furthermore, closely related variants of Stx2 also differ in pathogenic potential. Commercially available diagnostic tests for Shiga toxin distinguish between Shiga toxin variants based on antigenic differences, not pathogenic potential. Thus, a test that distinguishes between Shiga toxin variants based on pathogenic potential represents significant advancement in diagnostic and therapeutic value for affected patients.
Researchers at the University of Cincinnati have developed novel, glycoconjugate ligands which mimic the natural receptors and exhibit specific and differential binding toward Shiga toxin variants based on biological activity. These glycoconjugates can be used as robust, specific, high affinity ligands for the detection and possibly treatment of Shiga toxin mediated disease. Additionally, the methods used to make and screen these glycoconjugates represent a platform technology that can be applied to many other toxins, viruses and bacteria. A patent application has been filed that includes novel compositions, methods for making and methods for screening glycoconjugates.
Glycoconjugates distinguish Shiga toxin variants based on biological activity, not antigenicity and unlike antibodies, glycoconjugates are insensitive to genetic drift.
Glycoconjugates can be used in several assay platforms including ELISA and sensor arrays.
Glycoconjugates have superior thermal and chemical stability compared to antibodies.
No cross reactivity or false positives are expected with this class of compounds.