Chlamydia trachomatis suppresses host cell store-operated Ca(2+) entry and inhibits NFAT/calcineurin signaling

The obligate intracellular bacterium, Chlamydia trachomatis, replicates within a parasitophorous vacuole termed an inclusion. During development, host proteins critical for regulating intracellular calcium (Ca(2+)) homeostasis interact with the inclusion membrane. The inclusion membrane protein, MrcA, interacts with the inositol-trisphosphate receptor (IP(3)R), an ER cationic channel that conducts Ca(2+). Stromal interaction molecule 1 (STIM1), an ER transmembrane protein important for regulating store-operated Ca(2+) entry (SOCE), localizes to the inclusion membrane via an uncharacterized interaction. We therefore examined Ca(2+) mobilization in C. trachomatis infected cells. Utilizing a variety of Ca(2+) indicators to assess changes in cytosolic Ca(2+) concentration, we demonstrate that C. trachomatis impairs host cell SOCE. Ca(2+) 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.