CONICET | Buscador de Institutos y Recursos Humanos

Salmonella Typhimurium is a common pathogen associated to the development of acute diarrhea. How protease inhibitors present in Salmonella genome might contribute to the gut colonization and diarrhea development is poorly understood. Thus, using MEROPSdatabase plus the present literature for protease inhibitors we performed an in silico analysis and found 4 families of Salmonella protease inhibitors which might be involved in the ability of this bacteria to colonize the gut. Here we present preliminary results of Salmonellaprotease inhibitor knock-out strains in the in vivo streptomycin pretreated murine model. One-day post infection bacterial colonization and pathological changes of ceca were analyzed. In agreement with Barthel et al., upon infection with Wild Type (WT) strain, the ceca of mice were shriveled to a small size, pale and filled with purulent exudate and had reduced weight, while after infection with the protease inhibitor knock-out strains an attenuated phenotype was observed. Oral infection with WT strain lead to histopathological changes in the ceca of streptomycin treated mice: pronounced edema in thesubmucosa, edematous changes in the lamina propria, crypt elongation, disruption of the crypt architecture, reduced numbers of goblet cells, epithelial erosion and/or ulceration and pronounced PMN infiltration in the submucosa, lamina propria, and epithelial layer, aswell as transmigration of PMN into the intestinal lumen. In contrast, protease inhibitor knock-out strains showed attenuated capacity to make histopathological changes during infection. Altogether, these preliminary results suggest that protease inhibitors could contribute to the Salmonella Typhimurium pathogenesis and the development of colitis in vivo.