Strains of Escherichia coli producing
Shiga toxins Stx1, Stx2, Stx2c, and Stx2d cause
gastrointestinal disease and the
hemolytic-uremic syndrome in humans. We have recently constructed a recombinant bacterium which displays
globotriose (the receptor for these toxins) on its surface and adsorbs and neutralizes these
Shiga toxins with very high efficiency. This agent has great potential for the treatment of humans with such
infections. E. coli strains which cause
edema disease in pigs produce a variant toxin, Stx2e, which has a different receptor specificity from that for the other members of the Stx family. We have now modified the
globotriose-expressing bacterium such that it expresses
globotetraose (the preferred receptor for Stx2e) by introducing additional genes encoding a N-
acetylgalactosamine transferase and a UDP-N-acetylgalactosamine-4-epimerase. This bacterium had a reduced capacity to neutralize Stx1 and Stx2c in vitro, but remarkably, its capacity to bind Stx2e was similar to that of the
globotriose-expressing construct; both constructs neutralized 98.4% of the cytotoxicity in lysates of E. coli JM109 expressing cloned stx2e. These data suggest that either
globotriose- or
globotetraose-expressing constructs may be suitable for treatment and/or prevention of
edema disease in pigs.