Fig 6. Stx2 mediated inhibition of bovine intestinal epithelial proliferation.

Normal intestinal epithelial proliferation and differentiation (left) is driven by active stem cells located at the base of crypts. Stem cells continuously generate proliferating progeny that differentiate into the various cell lineages of mature intestinal villi and migrate up the crypt toward the villus tip. Continuous generation of new intestinal epithelial cells is balanced by apoptosis of older cells at the luminal surface resulting in the rapid turnover of intestinal epithelial cells. Expression and release of Stx2 into the intestinal crypt (right) by colonising Stx2+ EHEC O157 is proposed to inhibit normal stem cell driven proliferation. Inhibition may be direct by Stx2 binding to and inactivating Gb3+ stem cells or indirect inhibition of stem cells by interaction of Stx2 with as yet unidentified Gb3+ cells in the base of the crypt. E. coli O157 colonises at the luminal surface and further inhibits local epithelial turnover by type 3 secretion system-mediated delivery of specific effectors that can inhibit apoptosis.