The chlamydial organism S imkania negevensis forms ER vacuole contact sites and inhibits ER ‐stress

Summary Most intracellular bacterial pathogens reside within membrane‐surrounded host‐derived vacuoles. Few of these bacteria exploit membranes from the host's endoplasmic reticulum ( ER ) to form a replicative vacuole. Here, we describe the formation of ER –vacuole contact sites as part of the replicative niche of the chlamydial organism S imkania negevensis . Formation of ER –vacuole contact sites is evolutionary conserved in the distantly related protozoan host A canthamoeba castellanii . S imkania growth is accompanied by mitochondria associating with the S imkania ‐containing vacuole ( SCV ). Super‐resolution microscopy as well as 3 D reconstruction from electron micrographs of serial ultra‐thin sections revealed a single vacuolar system forming extensive ER – SCV contact sites on the S imkania vacuolar surface. S imkania infection induced an ER ‐stress response, which was later downregulated. Induction of ER ‐stress with T hapsigargin or T unicamycin was strongly inhibited in cells infected with S imkania . Inhibition of ER ‐stress was required for inclusion formation and efficient growth, demonstrating a role of ER ‐stress in the control of S imkania infection. Thus, S imkania forms extensive ER – SCV contact sites in host species evolutionary as diverse as human and amoeba. Moreover, S imkania is the first bacterial pathogen described to interfere with ER ‐stress induced signalling to promote infection.