The type III effector IpgD recodes Ca signals during invasion of epithelial cells.

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