A diet-specific microbiota drives Salmonella Typhimurium to adapt its in vivo response to plant-derived substrates.

BACKGROUND: Little is known about the complex interactions between the diet, the gut microbiota, and enteropathogens. Here, the impact of two specific diets on the composition of the mouse gut microbiota and on the transcriptional response of Salmonella Typhimurium (S. Typhimurium) was analyzed in an enteritis model. RESULTS: Mice were fed for two weeks a fibre-rich, plant-based diet (PD), or a Westernized diet (WD) rich in animal fat and proteins and in simple sugars, and then infected with an invasin-negative S. Typhimurium strain ST4/74 following streptomycin-treatment. Seventy-two hours post infection, fecal pathogen loads were equal in both diet groups, suggesting that neither of the diets had negatively influenced the ability of this ST4/74 strain to colonize and proliferate in the gut at this time point. To define its diet-dependent gene expression pattern, S. Typhimurium was immunomagnetically isolated from the gut content, and its transcriptome was analyzed. A total of 66 genes were more strongly expressed in mice fed the plant-based diet. The majority of these genes was involved in metabolic functions degrading substrates of fruits and plants. Four of them are part of the gat gene cluster responsible for the uptake and metabolism of galactitol and D-tagatose. In line with this finding, 16S rRNA gene amplicon analysis revealed higher relative abundance of bacterial families able to degrade fiber and nutritive carbohydrates in PD-fed mice in comparison with those nourished with a WD. Competitive mice infection experiments performed with strain ST4/74 and ST4/74 ΔSTM3254 lacking tagatose-1,6-biphosphate aldolase, which is essential for galactitol and tagatose utilization, did not reveal a growth advantage of strain ST4/74 in the gastrointestinal tract of mice fed plant-based diet as compared to the deletion mutant. CONCLUSION: A Westernized diet and a plant-based diet evoke distinct transcriptional responses of S. Typhimurium during infection that allows the pathogen to adapt its metabolic activities to the diet-derived nutrients. This study therefore provides new insights into the dynamic interplay between nutrient availability, indigenous gut microbiota, and proliferation of S. Typhimurium.

Comparison between Listeria sensu stricto and Listeria sensu lato strains identifies novel determinants involved in infection.

The human pathogen L. monocytogenes and the animal pathogen L. ivanovii, together with four other species isolated from symptom-free animals, form the "Listeria sensu stricto" clade. The members of the second clade, "Listeria sensu lato", are believed to be solely environmental bacteria without the ability to colonize mammalian hosts. To identify novel determinants that contribute to infection by L. monocytogenes, the causative agent of the foodborne disease listeriosis, we performed a genome comparison of the two clades and found 151 candidate genes that are conserved in the Listeria sensu stricto species. Two factors were investigated further in vitro and in vivo. A mutant lacking an ATP-binding cassette transporter exhibited defective adhesion and invasion of human Caco-2 cells. Using a mouse model of foodborne L. monocytogenes infection, a reduced number of the mutant strain compared to the parental strain was observed in the small intestine and the liver. Another mutant with a defective 1,2-propanediol degradation pathway showed reduced persistence in the stool of infected mice, suggesting a role of 1,2-propanediol as a carbon and energy source of listeriae during infection. These findings reveal the relevance of novel factors for the colonization process of L. monocytogenes.

Temperature- and nitrogen source-dependent regulation of GlnR target genes in Listeria monocytogenes.

The ubiquitous pathogen Listeria monocytogenes lives either saprophytically in the environment or within cells in a vertebrate host, thus adapting its lifestyle to its ecological niche. Growth experiments at 24 and 37 °C (environmental and host temperature) with ammonium or glutamine as nitrogen sources revealed that ammonium is the preferred nitrogen source of L. monocytogenes. Reduced growth on glutamine is more obvious at 24 °C. Global transcriptional microarray analyses showed that the most striking difference in temperature-dependent transcription was observed for central nitrogen metabolism genes, glnR (glutamine synthetase repressor GlnR), glnA (glutamine synthetase GlnA), amtB (ammonium transporter AmtB), glnK (PII regulatory protein GlnK), and gdh (glutamate dehydrogenase) when cells were grown on glutamine. When grown on ammonium, both at 24 and 37 °C, the transcriptional level of these genes resembles that of cells grown with glutamine at 37 °C. Electrophoretic mobility shift assay studies and qPCR analyses in the wild-type L. monocytogenes and the deletion mutant L. monocytogenes ∆glnR revealed that the transcriptional regulator GlnR is directly involved in temperature- and nitrogen source-dependent regulation of the respective genes. Glutamine, a metabolite known to influence GlnR activity, seems unlikely to be the (sole) intracellular signal mediating this temperature-and nitrogen source-dependent metabolic adaptation.