The chlamydial organism Simkania negevensis forms ER vacuole contact sites and inhibits ER-stress

Adrian Mehlitz, Karthika Karunakaran, Jo-Ana Herweg, Georg Krohne, Sebastian van de Linde, Elke Rieck, Markus Sauer, Thomas Rudel

Research output: Contribution to journalArticle

31 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1224-1243
Number of pages20
JournalCellular Microbiology
Volume16
Issue number8
Early online date21 Mar 2014
DOIs
Publication statusPublished - 26 Jul 2014
Externally publishedYes

Keywords

  • vacuoles
  • endoplasmic reticulum
  • ER–vacuole contact
  • super-resolution microscopy
  • electron micrographs
  • Thapsigargin
  • Tunicamycin
  • ER-stress
  • Simkania negevensis
  • Chlamydia

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