Institute of Molecular Infection Biology
University of Würzburg
Tel.: 0931 31 82575
Fax: 0931 31 82578
RNA Biology, Infection Biology, Microbiology
Primate-restricted Salmonella enterica serovar Typhi (S. Typhi) causes life-threatening typhoid fever while S. Typhimurium has a broad host-range and causes non-typhoidal intestinal infections and enteritis in humans. Both infect their hosts via the gastrointestinal route, exhibit a facultative intracellular life-style, and extensively manipulate host immune signaling. However, S. Typhi interactions with human host cells remain little understood due to the limited availability of primate infection models. Jörg Vogel and Heike Walles/Marco Metzger have been establishing a 3D in vitro human infection model mimicking the gastrointestinal barrier, utilizing an acellularized matrix of porcine gut fixed in a cell-crown. S. Typhimurium applied to the apical compartment followed by flow cytometry yields robust infection of the epithelial cell layer and low-level transmission of the bacteria across the intestinal barrier. They now plan to use vascularized primary intestinal tissue models kept under dynamic culture conditions and will supplement the vascular compartment with purified human peripheral blood leukocytes to understand their role in dissemination of Salmonella. The ultimate goal is to challenge the human in vitro infection model with S. Typhi and use dual RNA-Seq to simultaneously resolve human and pathogen transcriptomic changes as the infection progresses.