Chlamydia trachomatis suppresses host cell store-operated Ca2+ entry and inhibits NFAT/calcineurin signaling

Abstract

The obligate intracellular bacterium, Chlamydia trachomatis, replicates within a parasitophorous vacuole termed an inclusion. During development, host proteins critical for regulating intracellular calcium (Ca²⁺) homeostasis interact with the inclusion membrane. The inclusion membrane protein, MrcA, interacts with the inositol-trisphosphate receptor (IP₃R), an ER cationic channel that conducts Ca²⁺. Stromal interaction molecule 1 (STIM1), an ER transmembrane protein important for regulating store-operated Ca²⁺ entry (SOCE), localizes to the inclusion membrane via an uncharacterized interaction. We therefore examined Ca²⁺ mobilization in C. trachomatis infected cells. Utilizing a variety of Ca²⁺ indicators to assess changes in cytosolic Ca²⁺ concentration, we demonstrate that C. trachomatis impairs host cell SOCE. Ca²⁺ regulates many cellular signaling pathways. We find that the SOCE-dependent NFAT/calcineurin signaling pathway is impaired in C. trachomatis infected HeLa cells and likely has major implications on host cell physiology as it relates to C. trachomatis pathogenesis.