Spatio-temporal expression of the PagN Salmonella entry factor in the three commonly used murine models
Résumé
Salmonella are among the top-ranked foodborne pathogens, inducing a wide variety of diseases ranging from gastroenteritis to typhoid fever, depending on the infecting serovar, the host and its genetic background. As a facultative intracellular pathogen, Salmonella can induce its own internalization and survive either in a vacuole or in the cytosol in phagocytic and non-phagocytic cells through several virulence factors. Among them, the widely conserved PagN protein of Salmonella Typhimurium is both an invasin operating through a Zipper-like mechanism following interaction with heparan-sulfateproteoglycans (HSPG) and 1 integrin [1, 2] and an evasin (Holbert et al., in preparation). In this study, we aimed to precisely determine the kinetics of expression of PagN in mice using bioluminescence imaging [3]. S. Typhimurium reporter strains were constructed to follow pagN transcription in murine models reproducing the three main pathologies induced by Salmonella, i.e. typhoid fever, gastroenteritis and asymptomatic carriage. We observed a transcription of pagN in the intestine independently of the genetic background of the host and the inflammatory state of the animals. However, differences in the kinetics were observed in this organ depending of the animal model. Moreover, pagN transcription was detected at later time points in lymphoid organs following the systemic spread of the pathogen in the typhoid fever and gastroenteritis models. Further analyses based on the kinetics observed in this study and focusing on the identification of the cells targeted by PagN in the different mouse models, are in progress using flow cytometry, fluorescence-activated cell sorting, confocal microscopy and immuno-histochemistry