Transcytosis pathways used by Salmonella enterica and Mycobacterium avium for translocation across the intestinal epithelial barrier

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The intestinal epithelium is responsible for nutrient uptake and fluid balance, but also exhibits essential functions as a physical and innate immune barrier devoted to protecting the body against invasion of both commensal and pathogenic microorganisms. Many pathogens have evolved mechanisms that enable them to breach the epithelial barrier subverting host cell functions in order to survive, replicate, and disseminate. Salmonella and mycobacteria are important human and animal pathogens. Also, some pathogenic mycobacterial species such as the M. avium subspecies are enteroinvasive and use the intestinal tract as port of entry. Common to Samonella and M. avium subspecies is their capacity to target different types of intestinal epithelial cells for host entry. For both pathogens this might be of utmost importance since the type of cell used for translocation might considerably determine the next steps of the infection process. In this proposal we are focusing on the mechanisms of transcytosis of Salmonella and M. avium across the intestinal epithelium with special regard to the transcytotic compartments and exocytosis pathways. We aim to determine how Salmonella enterica serovars and different M. avium subspecies pass through and exit from polarized intestinal epithelial cells and characterize host cell pathways and the bacterial factors involved.