Shiga toxin 1 and 2 are the major virulence factors of E. coli O157:H7 and other entero-hemorrhagic E. coli strains, which are known to cause bloody diarrhea which proceeds to a life threatening sequelae, hemolytic uremic syndrome (HUS). Shiga toxins belong to AB5 family of toxins and the pentameric B-subunit of both the toxins is reported to recognize the Pk-trisaccharide portion of the globotriaosylceramide (Gb3) receptor to invade cells.  Stx2 has been found to be more toxic than Stx1, but the reason for the difference in toxicity has not been well established. In an effort to understand the difference in toxicity, a panel of synthetic oligosaccharide receptor mimics has been synthesized based on the structure of the Pk-trisaccharide, and NHAc-Pk-trisaccharide which have been previously shown to differentiate between Stx1 and Stx2. To our surprise the newly synthesized Pk-trisaccharide and NHAc-Pk-trisaccharide analogs did not show binding to any of the Shiga toxin variants. In addition the NHAc-Pk trisaccharide, which binds to Stx2 variants, Stx2a and Stx2c, did not bind to Stx2d, which is reported to be as toxic as Stx2a. Our binding studies have shown also that the toxins need to engage more than four trisacharrides for effective binding.

Binding affinity of Shiga toxin variants with Pk-trisaccharide analogs of globotriaosylceramide (Gb3)

244th National Meeting (2012)

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