The Shigella type III effector IpgD recodes Ca2+ signals during invasion of epithelial cells

Abstract The role of second messengers in the diversion of cellular processes by pathogens remains poorly studied despite their importance. Among these, Ca 2+ virtually regulates all known cell processes, including cytoskeletal reorganization, inflammation, or cell death pathways. Under physiological conditions, cytosolic Ca 2+ increases are transient and oscillatory, defining the so‐called Ca 2+ code that links cell responses to specific Ca 2+ oscillatory patterns. During cell invasion, Shigella induces atypical local and global Ca 2+ signals. Here, we show that by hydrolyzing phosphatidylinositol‐(4,5)bisphosphate, the Shigella type III effector IpgD dampens inositol‐(1,4,5)trisphosphate (InsP 3 ) levels. By modifying InsP 3 dynamics and diffusion, IpgD favors the elicitation of long‐lasting local Ca 2+ signals at Shigella invasion sites and converts Shigella ‐induced global oscillatory responses into erratic responses with atypical dynamics and amplitude. Furthermore, IpgD eventually inhibits InsP 3 ‐dependent responses during prolonged infection kinetics. IpgD thus acts as a pathogen regulator of the Ca 2+ code implicated in a versatility of cell functions. Consistent with this function, IpgD prevents the Ca 2+ ‐dependent activation of calpain, thereby preserving the integrity of cell adhesion structures during the early stages of infection.