Shigella flexneri subverts host polarized exocytosis to enhance cell‐to‐cell spread

Shigella flexneri is a gram‐negative bacterial pathogen that causes dysentery. Critical for disease is the ability of Shigella to use an actin‐based motility (ABM) process to spread between cells of the colonic epithelium. ABM transports bacteria to the periphery of host cells, allowing the formation of plasma membrane protrusions that mediate spread to adjacent cells. Here we demonstrate that efficient protrusion formation and cell‐to‐cell spread of Shigella involves bacterial stimulation of host polarized exocytosis. Using an exocytic probe, we found that exocytosis is locally upregulated in bacterial protrusions in a manner that depends on the Shigella type III secretion system. Experiments involving RNA interference (RNAi) indicate that efficient bacterial protrusion formation and spread require the exocyst, a mammalian multi‐protein complex known to mediate polarized exocytosis. In addition, the exocyst component Exo70 and the exocyst regulator RalA were recruited to Shigella protrusions, suggesting that bacteria manipulate exocyst function. Importantly, RNAi‐mediated depletion of exocyst proteins or RalA reduced the frequency of protrusion formation and also the lengths of protrusions, demonstrating that the exocyst controls both the initiation and elongation of protrusions. Collectively, our results reveal that Shigella co‐opts the exocyst complex to disseminate efficiently in host cell monolayers. Shigella flexneri, the cause of bacterial dysentery, disseminates in the intestinal epithelium by producing protrusive structures in the plasm membrane of human cells. Here we show that protrusion formation and spread of Shigella involves the exploitation of a multiprotein human complex called the “exocyst”. This complex mediates polarized exocytosis, which likely provides a membrane for the initiation and/or growth of protrusions.