IpaC of Shigella binds to the C-terminal domain of beta-catenin.

IpaC of Shigella is essential for initial bacterial entry into epithelial cells. We report here that IpaC interacts with beta-catenin and destabilizes the cadherin-mediated cell adhesion complex. Using a yeast two-hybrid system, we identified beta-catenin as a binding partner of IpaC within the host cell after cell entry, but not in the initial entry. Co-immunoprecipitation, confocal microscopy, and GST pull-down experiments confirmed the intracellular and cell-free interactions between these two proteins. The interaction sites were mapped to the ninth armadillo repeat of beta-catenin and to the C-terminus of IpaC. IpaC-associated beta-catenin was phosphorylated at tyrosine residues. This phosphorylation led to the destabilization of the functional cadherin-catenin complex, which could be a mechanism whereby the epithelial cell-cell tight adhesion is disrupted. These events may facilitate the further basolateral invasion of bacteria through the disrupted space and/or modulate the cell-to-cell spread of Shigella.