An orally applicable Shiga toxin neutralizer functions in the intestine to inhibit the intracellular transport of the toxin.

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We found that PPP-tet, a peptide-based Stx2 inhibitor, completely inhibited fluid accumulation in the rabbit ileum caused by the direct injection of Stx2. We also found that PPP-tet accumulated in the ileal epithelial cells only through its formation of a complex with Stx2. The complex in cultured epithelial cells blocked the intracellular transport of Stx2 from the Golgi apparatus to the endoplasmic reticulum, the process that is essential for Stx2 cytotoxicity. Our results reveal that PPP-tet functions as a potent Stx neutralizer in the intestine by altering the intracellular transport of Stx2 in epithelial cells.