title: The chlamydial organism Simkania negevensis forms ER vacuole contact sites and inhibits ER-stress.
abstract: 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 Simkania negevensis. Formation of ER-vacuole contact sites is evolutionary conserved in the distantly related protozoan host Acanthamoeba castellanii. Simkania growth is accompanied by mitochondria associating with the Simkania-containing vacuole (SCV). Super-resolution microscopy as well as 3D reconstruction from electron micrographs of serial ultra-thin sections revealed a single vacuolar system forming extensive ER-SCV contact sites on the Simkania vacuolar surface. Simkania infection induced an ER-stress response, which was later downregulated. Induction of ER-stress with Thapsigargin or Tunicamycin was strongly inhibited in cells infected with Simkania. Inhibition of ER-stress was required for inclusion formation and efficient growth, demonstrating a role of ER-stress in the control of Simkania infection. Thus, Simkania forms extensive ER-SCV contact sites in host species evolutionary as diverse as human and amoeba. Moreover, Simkania is the first bacterial pathogen described to interfere with ER-stress induced signalling to promote infection.
authors: University of Wuerzburg, Biocenter, Department of Microbiology, Am Hubland, D-97074, Wuerzburg, Germany.
authors: Adrian
authors: A
authors: Mehlitz
authors: Karthika
authors: K
authors: Karunakaran
authors: Jo-Ana
authors: JA
authors: Herweg
authors: Georg
authors: G
authors: Krohne
authors: Sebastian
authors: S
authors: van de Linde
authors: Elke
authors: E
authors: Rieck
authors: Markus
authors: M
authors: Sauer
authors: Thomas
authors: T
authors: Rudel
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002694:Chlamydiaceae Infections / Q000473:pathology; D002695:Chlamydiales / Q000472:pathogenicity*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology; D014415:Tunicamycin / Q000494:pharmacology; D014617:Vacuoles / Q000382:microbiology*
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D014415:Tunicamycin; D019284:Thapsigargin