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Mathias Hornef (2014-2017)

In vivo Formation and Maintenance of Salmonella-Containing Vacuoles (SCVs) in Enterocytes using a Novel Neonatal Mouse Model

Invasion of non-phagocytic cells by the human pathogen Salmonella enterica and the manipulation of the endosomal compartment to allow intracellular bacterial survival and proliferation have been studied extensively in vitro. However, establishment of the Salmonella-containing vacuole (SCV) in non-phagocytic cells such as epithelial cells has not been investigated in vivo due to the lack of a suitable animal model. Based on the establishment of a new infection model of neonate mice that allows the analysis of enterocyte invasion and SCV formation in vivo, the present research project aims at characterizing this endosomal compartment in primary enterocytes during the course of infection. We will define host and bacterial factors that prevent membrane disruption, and contribute to SCV formation and intraepithelial trafficking to facilitate bacterial proliferation and mucosal translocation.

The planned research project addresses the following issues:

(i) Detailed characterization of Salmonella-containing vacuoles (SCV) in fully differentiated enterocytes in vivo and in infected organoid co-cultures.

(ii) Analysis of the role of Salmonella effector proteins for SCV generation and vesicular trafficking within polarized primary enterocytes.

(iii) Identification of host-derived signals that contribute to SCV formation or mediate endosomal disruption and bacterial killing.

We expect that this first analysis of the establishment of Salmonella-containing vacuoles in enterocytes in vivo will reveal new and important insight in the intracellular host-microbial interaction and pathogenesis of Salmonella infection.