Shigella flexneri disruption of host cell-cell tension promotes intercellular spread

Abstract

During infection, a subset of bacterial pathogens invades into the eukaryotic cytosol and spreads between cells of an epithelial layer. This intercellular spread is essential for disease and requires actin-based motility leading to the formation of plasma membrane protrusions. Protrusions are engulfed by the adjacent cell in an active process requiring both bacterial and eukaryotic proteins. Here, we demonstrate that the Shigella spp. type 3 secretion system protein IpaC promotes bacterial spread by reducing intercellular tension. S. flexneri producing a point mutant of IpaC that cannot interact with the cell-cell adhesion protein {beta}-catenin were unable to reduce intercellular tension, form protrusions, or spread, demonstrating that interaction of IpaC with {beta}-catenin is required for these processes. Spread was restored by chemical reduction of intercellular tension or genetic depletion of {beta}-catenin. This work defines a molecular mechanism by which Shigella overcomes host cell-cell tension to mediate spread.