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, Ca²⁺ virtually regulates all known cell processes, including cytoskeletal reorganization, inflammation, or cell death pathways. Under physiological conditions, cytosolic Ca²⁺ increases are transient and oscillatory, defining the so-called Ca²⁺ code that links cell responses to specific Ca²⁺ oscillatory patterns. During cell invasion, Shigella induces atypical local and global Ca²⁺ signals. Here, we show that by hydrolyzing phosphatidylinositol-(4,5)bisphosphate, the Shigella type III effector IpgD dampens inositol-(1,4,5)trisphosphate (InsP₃) levels. By modifying InsP₃ dynamics and diffusion, IpgD favors the elicitation of long-lasting local Ca²⁺ signals at Shigella invasion sites and converts Shigella-induced global oscillatory responses into erratic responses with atypical dynamics and amplitude. Furthermore, IpgD eventually inhibits InsP₃-dependent responses during prolonged infection kinetics. IpgD thus acts as a pathogen regulator of the Ca²⁺ code implicated in a versatility of cell functions. Consistent with this function, IpgD prevents the Ca²⁺-dependent activation of calpain, thereby preserving the integrity of cell adhesion structures during the early stages of infection.

Keywords: Shigella; IpgD; calcium; calpain; talin.