Divergent Roles of Salmonella Pathogenicity Island 2 and Metabolic Traits during Interaction of S. enterica Serovar Typhimurium with Host Cells

The molecular mechanisms of virulence of the gastrointestinal pathogen Salmonella enterica are commonly studied using cell culture models of infection. In this work, we performed a direct comparison of the interaction of S. enterica serovar Typhimurium (S. Typhimurium) with the non-polarized epithelial cell line HeLa, the polarized cell lines CaCo2, T84 and MDCK, and macrophage-like RAW264.7 cells. The ability of S. Typhimurium wild-type and previously characterized auxotrophic mutant strains to enter host cells, survive and proliferate within mammalian cells and deploy the Salmonella Pathogenicity Island 2-encoded type III secretion system (SPI2-T3SS) was quantified. We found that the entry of S. Typhimurium into polarized cells was much more efficient than entry into non-polarized cells or phagocytic uptake. While SPI2-T3SS dependent intracellular proliferation was observed in HeLa and RAW cells, the intracellular replication in polarized cells was highly restricted and not affected by defective SPI2-T3SS. The contribution of aromatic amino acid metabolism and purine biosynthesis to intracellular proliferation was distinct in the various cell lines investigated. These observations indicate that the virulence phenotypes of S. Typhimurium are significantly affected by the cell culture model applied

Hydrogen sulfide inhibits IL-8 expression in human keratinocytes via MAP kinase signaling

Sulfur is able to penetrate the skin, and a sulfur-rich balneotherapy has been suggested to be effective in the treatment of psoriasis. Psoriasis is now considered a genetically programmed, immune-mediated, inflammatory disease, in which intralesional T lymphocytes trigger keratinocytes to proliferate and perpetuate the disease process. Interleukin (IL)-17 and IL-22 produced by Th1/Th17 lymphocytes induce IL-8 secretion by keratinocytes, a key event in the pathogenesis of the disease. It is now clear that mitogen-activated protein kinase (MAPK) (extracellular signal-regulated kinases (ERK) 1 and 2) activity is required for IL-17-induced IL-8 synthesis by keratinocytes, and, in fact, MAPK activity is increased in lesional psoriatic skin. Here, we demonstrate both in vitro and in vivo on primary psoriatic lesions that pharmacological inhibitors of ERKs as well as hydrogen sulfide not only reduce the basal expression and secretion of IL-8, but also interfere with IL-17- and IL-22-induced IL-8 production. These observations, together with the known anti-inflammatory activity of H2S, are relevant to understanding some previously unexplained biological effects exerted by sulfur therapy

Genetics and genomics of carrot sugars and polyacetylenes

Carrot root carbohydrates, composed mainly of reducing and non-reducing free sugars, influence flavor, total dissolved solids and dry mater content, all quality traits for fresh-market and processing carrots. In the last decades, important advances have been made in biochemistry, physiology and genetics of carrot sugar metabolism. Several enzymes involved in sucrose metabolism and their corresponding genes have been isolated and functionally characterized, increasing our understanding of their individual roles and of their interactions in complex regulatory systems that influence major plant physiological processes, including partitioning of photoassimilates, plant growth and storage of different sugar types in the carrot tap root. Polyacetylenes represent a large group of non-volatile lipid compounds produced primarily by members of the Apiaceae family. The major carrot polyacetylenes have been extensively studied with regards to their analytical identification and elucidation of their chemical structures as well as their biological activities, which have revealed numerous health-promoting properties for these compounds. Very recently, with the publication of the carrot genome sequence and related genomic and transcriptomic sequence resources, key genes and enzymes involved in the biosynthesis of carrot polyacetylenes were discovered. In this chapter, advances in genetics and genomics of carrot sugars and polyacetylenes were reviewed and discussed.Fil: Cavagnaro, Pablo Federico. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Mendoza-San Juan. Estación Experimental Agropecuaria La Consulta; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Departamento de Producción Agropecuaria. Cátedra de Horticultura y Floricultura; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentin