Search

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 Thapsigargin or Tunicamycin 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. [ABSTRACT FROM AUTHOR]

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., (© 2014 John Wiley & Sons Ltd.)