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 L2 infected HeLa cells and likely has major implications on host cell physiology as it relates to C. trachomatis pathogenesis.

Chlamydia trachomatis effectors target the mitochondria and alter mitochondrial protein composition

“…Inositol 1,4,5-triphosphate receptor interacts with the mitochondrial outer membrane porin, VDAC ( v oltage- d ependent a nion c hannel type 1), resulting in Ca 2+ efflux into the mitochondria [58]. The inositol 1,4,5-triphosphate receptor(s) are known to be recruited to the inclusion membrane by microdomain Inc, MrcA, which may explain their absence in the infected proteome [59, 60]. This report contributes to a growing body of knowledge within the field detailing the variety of mechanisms Chlamydia spp.…”