Transcriptome and proteome analysis of Salmonella enterica serovar Typhimurium systemic infection of wild type and immune-deficient mice

Abstract

Salmonella enterica are a threat to public health. Current vaccines are not fully effective. The ability to grow in infected tissues within phagocytes is required for S. enterica virulence in systemic disease. As the infection progresses the bacteria are exposed to a complex host immune response. Consequently, in order to continue growing in the tissues, S. enterica requires the coordinated regulation of fitness genes. Bacterial gene regulation has so far been investigated largely using exposure to artificial environmental conditions or to in vitro cultured cells, and little information is available on how S. enterica adapts in vivo to sustain cell division and survival. We have studied the transcriptome, proteome and metabolic flux of Salmonella, and the transcriptome of the host during infection of wild type C57BL/6 and immune-deficient gp91-/-phox mice. Our analyses advance the understanding of how S. enterica and the host behaves during infection to a more sophisticated level than has previously been reported.

The metabolic pathways utilized by Salmonella Typhimurium during infection of host cells

“…The proteomic studies, combined with genomics and results from mutants have in some cases been combined to infer metabolic networks for S . Typhimurium within infected host cells and murine tissues (Becker et al ., ; Raghunathan et al ., ; Oshota et al ., ). In tissue extraction, it is assumed that the enzymes are active within bacteria from the extracted tissues and are representative of the nutrient availability and the metabolism of the bacterium at the time of extraction.…”

“…An SV40 transformed murine intestinal epithelial colon cell line, mIC cl2 (Bens et al, 1996), has also been used (Garcia-Gutierrez et al, 2016). In addition to infection assays using metabolic mutants, genome-wide proteomic studies have been performed in murine infection models using BALB/c, C57BL/6 or gp91 -/phox mouse lines (Becker et al, 2006;Oshota et al, 2017).…”

“…Isotopologue studies using labelled precursors, typically [U-13 C 6 ] glucose, have been used to determine the metabolic profile of both S. Typhimurium wild-type and mutant strains impaired in the uptake of glucose and mannose and/or glucose 6-phosphate within tissue cultured Caco-2 host cells Eisenreich et al, 2010). The proteomic studies, combined with genomics and results from mutants have in some cases been combined to infer metabolic networks for S. Typhimurium within infected host cells and murine tissues (Becker et al, 2006;Raghunathan et al, 2009;Oshota et al, 2017). In tissue extraction, it is assumed that the enzymes are active within bacteria from the extracted tissues and are representative of the nutrient availability and the metabolism of the bacterium at the time of extraction.…”

The anti-Salmonella and immunostimulatory properties of yeast-based postbiotics in poultry and cattle

“…Once the Salmonella are intracellular, the pathogen subverts immune surveillance which reduces inflammatory pathway activation and xenophagy. In order to evade the immune system, the intracellular survival of Salmonella requires a series of orchestrated and well-timed T3SS-mediated events (Ciraci et al, 2010;Oshota et al, 2017;Razzuoli et al, 2017;van Hemert et al, 2006). There are two main pathogenicity islands required: SPI-1, whose second-stage induction suppresses the intracellular detection of Salmonella; and, SPI-2-mediated quiescence of the SCV (Keestra-Gounder et al, 2015).…”

“…These synergistic pathways likely converge on MAPK and lead to a successful immune response to Salmonella (Sarma, 2012). In host-restricted serovars of Salmonella, gene loss events lead to a reduction of inflammation that facilitates the ability of Salmonella to successfully evade the immune system (Foley et al, 2013;Golubeva et al, 2012;Klerks et al, 2007;Knodler, 2015;Oshota et al, 2017;Razzuoli et al, 2017;Selander et al, 1992). This is likely due to a highly tuned activation of its T3SS (Diepold and Armitage, 2015;Raymond et al, 2013;Velge et al, 2012).…”