ATP-Mediated Erk1/2 Activation Stimulates Bacterial Capture by Filopodia, which Precedes Shigella Invasion of Epithelial Cells

SummaryShigella, the causative agent of bacillary dysentery in humans, invades epithelial cells, using a type III secretory system (T3SS) to inject bacterial effectors into host cells and remodel the actin cytoskeleton. ATP released through connexin hemichanels on the epithelial membrane stimulates Shigella invasion and dissemination in epithelial cells. Here, we show that prior to contact with the cell body, Shigella is captured by nanometer-thin micropodial extensions (NMEs) at a distance from the cell surface, in a process involving the T3SS tip complex proteins and stimulated by ATP- and connexin-mediated signaling. Upon bacterial contact, NMEs retract, bringing bacteria in contact with the cell body, where invasion occurs. ATP stimulates Erk1/2 activation, which controls actin retrograde flow in NMEs and their retraction. These findings reveal previously unappreciated facets of interaction of an invasive bacterium with host cells and a prominent role for Erk1/2 in the control of filopodial dynamics.

► Bacterial capture by filopodia precedes Shigella epithelial invasion
► Filopodial capture involves the Shigella T3SS tip complex proteins IpaB and IpaD
► ATP-mediated signaling stimulates filopodial capture and invasion
► Actin dynamics, controlled by Erk1/2, drives filopodial retraction and subsequent invasion