<i>Escherichia coli</i>Shiga toxins induce apoptosis in epithelial cells that is regulated by the Bcl-2 family

Human intestinal cells lack globotriaosylceramide (Gb3), the receptor for Shiga toxin-1 (Stx1) and Shiga toxin-2 (Stx2). Therefore, the role of these toxins in mediating intestinal disease during infection with Shiga toxin-producing Escherichia coli is unclear. The aims of this study were to determine whether Stx1 and Stx2 induce apoptosis in epithelial cells expressing (HEp-2, Caco-2) or lacking (T84) Gb3and to characterize the role of the Bcl-2 family. Stx1 (12.5 ng/ml) induced apoptosis in both HEp-2 (21.9 ± 7.9% vs. 0.8 ± 0.3%, P = 0.01) and Caco-2 (10.1 ± 1.2% vs. 3.1 ± 0.4%, P = 0.006) cells but not in Gb3-deficient T84 cells. Toxin-mediated apoptosis of HEp-2 cells was associated with enhanced expression of the proapoptotic protein Bax. Inhibition of caspase activation prevented toxin-stimulated apoptosis. In addition, overexpression of Bcl-2 by transient transfection blocked Stx1-stimulated cell death. These findings indicate that Shiga toxins produced by E. coli signal Gb3-expressing epithelial cells to undergo apoptosis in association with enhanced Bax expression, thereby resulting in activation of the caspase cascade.

Escherichia coliShiga toxins induce apoptosis in epithelial cells that is regulated by the Bcl-2 family Journal Articles