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Thomas Rudel (2011-2017)

Formation and transport of Simkania negevensis vacuole and modulation of host cell signal transduction

Obligate intracellular bacteria of the order Chlamydiales establish and maintain their replicative vacuole in host cells. The Chlamydia-like organism Simkania negevensis constitutes an evolutionary link between the environmental Chlamydia and the human pathogenic C. trachomatis and C. pneumoniae since it efficiently replicates in typical host cells of both amoebae and human cells, respectively. We have demonstrated that Simkaniais closely associated with the host's endoplasmic reticulum (ER) and mitochondria. Formation of the Simkania containing vacuole (SCV) is accompanied by the formation of extensive ER-SCV contact sites both in the protozoan host Acanthamoeba castellanii as well as in human cells. Simkania infection interfered with the host ER-stress response to establish the SCV and maintain efficient bacterial replication. We will investigate the mechanism of SCV formation and how the interaction with the host ER and mitochondria contributes to establish Simkania infections. As Simkania is the first example of a bacterial pathogen that downregulates ER-stress, we will use this as a model to investigate the mechanisms of interference and how this impacts on the previously described capacity of Simkania to inhibit apoptosis signaling. Candidate bacterial factors identified in the first round of SPP1580 will be investigated for their role in the interaction of Simkania with host cell organelles. We aim to further investigate the biology of the SCV and its intimate crosstalk to the host ER and mitochondria.