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Nutrient utilization capabilities of <i>Salmonella</i> in infected mouse tissues.
No full text<p>Colored names represent transporters and enzymes that were detected in <i>Salmonella</i> purified from mouse spleen (<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003301#ppat.1003301.s007" target="_blank">Table S1</a>). The color shows enzyme abundance in copies per <i>Salmonella</i> cell. Grey proteins were not detected. Arrows represent metabolic reactions. Transport reactions are labeled with cylinders. Arrow colors show maximal catalytic capacities calculated from enzyme abundance and reported turnover numbers (<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003301#ppat.1003301.s008" target="_blank">Table S2</a>). Grey arrows represent reactions, for which enzymes were not detected and/or turnover numbers were unavailable. Tsx is an outer membrane general nucleoside channel; NupC is a high affinity transporter for all nucleosides except guanosine and deoxyguanosine. An interactive map with detailed description of all detected metabolic capabilities is available at <a href="http://www.biozentrum.unibas.ch/personal/bumann/steeb_et_al/index.html" target="_blank">http://www.biozentrum.unibas.ch/personal/bumann/steeb_et_al/index.html</a>.</p
Intestinal inflammation responds to microbial tissue load independent of pathogen/non-pathogen discrimination
Get PDFThe intestinal immune system mounts inflammatory responses to pathogens but tolerates harmless commensal microbiota. Various mechanisms for pathogen/non-pathogen discrimination have been proposed but their general relevance for inflammation control is unclear. Here, we compared intestinal responses to pathogenic Salmonella and non-pathogenic E. coli. Both microbes entered intestinal Peyer's patches and, surprisingly, induced qualitatively and quantitatively similar initial inflammatory responses revealing a striking discrimination failure. Diverging inflammatory responses only occurred when Salmonella subsequently proliferated and induced escalating neutrophil infiltration, while harmless E. coli was rapidly cleared from the tissue and inflammation resolved. Transient intestinal inflammation induced by harmless E. coli tolerized against subsequent exposure thereby preventing chronic inflammation during repeated exposure. These data revealed a striking failure of the intestinal immune system to discriminate pathogens from harmless microbes based on distinct molecular signatures. Instead, appropriate intestinal responses to gut microbiota might be ensured by immediate inflammatory responses to any rise in microbial tissue loads, and desensitization after bacterial clearance
Schematic overview of host nutrient supply for intracellular pathogens (blue, cytosolic pathogen; green, vacuolar pathogen; AA, amino acids; Glc, glucose; Glyc, glycerol).
No full text<p>Cellular mechanisms that convert polymeric nutrients into small building blocks and deliver them to vacuolar pathogens are shown on the right (1, degradation of proteins to amino acids by proteasomes; 2, endocytosis and degradation in lysosomes; 3, autophagosome formation and delivery to lysosomes; 4, vesicle trafficking and fusion/luminal exchange with pathogen-containing vacuole). Pathways that are stimulated (+) or repressed during hypoxic conditions within inflammatory foci are labelled in purple.</p
Main energy sources of intracellular pathogens.
No full text<p>Main energy sources of intracellular pathogens.</p
A quantitative genome-scale model of <i>Salmonella</i> nutrition, metabolism, and growth in infected mouse spleen.
No full text<p>This schematic map shows available host nutrients, their respective uptake rates represented by color and font size, and their conversion to new <i>Salmonella</i> biomass through the <i>Salmonella</i> metabolic network (see text and <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003301#ppat.1003301.s012" target="_blank">Tables S6</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003301#ppat.1003301.s013" target="_blank">S7</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003301#ppat.1003301.s014" target="_blank">S8</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003301#ppat.1003301.s015" target="_blank">S9</a> for detailed explanation and quantitative values). Symbols represent metabolites (squares, carbohydrates; pointing up triangles, amino acids; vertical ellipses, purines; horizontal ellipses, pyrimidines; pointing down triangles, cofactors; tees, tRNAs; circles, other metabolites; filled symbols, phosphorylated metabolites) and proteins (diamonds). The connecting lines present metabolic reactions. The brown lines represent the inner and outer membranes. An interactive map with detailed annotation of all reactions and the computational model in SBML format are available at <a href="http://www.biozentrum.unibas.ch/personal/bumann/steeb_et_al/index.html" target="_blank">http://www.biozentrum.unibas.ch/personal/bumann/steeb_et_al/index.html</a>. The model is also available in the supporting information (<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003301#ppat.1003301.s019" target="_blank">Model S1</a>).</p
Administration of harmless bacteria induces rapid tolerance to non-pathogenic and pathogenic gut bacteria.
No full text<p><b>A</b>) Neutrophil infiltration in murine Peyer’s patches 3 h after the last of one, two, or three daily doses of probiotic <i>EcN</i> to BALB/c mice. Neutrophils numbers in control mice that received only PBS are also shown. Similar data were obtained in two independent experiments. <b>B</b>) Neutrophil accumulation in Peyer’s patches two days after oral infection with pathogenic <i>Salmonella</i> in wildtype C57BL/6 mice (B6) and mutant mice deficient in TLR2. One day before <i>Salmonella</i> infection, mice received PBS (open circles), or a single dose of live (filled circles) or formalin-fixed (filled triangles) <i>EcN</i>. Similar data were obtained in one independent experiment. <b>C</b>) Neutrophil accumulation in Peyer’s patches two days after oral infection with pathogenic <i>Salmonella</i> in BALB/c mice. One day before <i>Salmonella</i> infection, mice received PBS (open circles), or a single dose of avirulent live <i>Salmonella aroA asd</i> (filled circles). Pooled data from two independent experiments are shown. Significance of differences between groups was determined using t-test (***, <i>P</i><0.001; **, <i>P</i><0.01; *, <i>P</i><0.05).</p
Initial inflammatory responses to <i>Salmonella</i> are independent of specific virulence factors.
No full text<p><b>A</b>) PMN infiltration 3 h post administration of various live <i>Salmonella</i> mutants in BALB/c mice. Data for formalin (FA) killed wildtype <i>Salmonella</i> are also shown. Significance of differences to baseline levels (open circles) was determined using t-test on log-transformed data (***, <i>P</i><0.001; **, <i>P</i><0.01; *, <i>P</i><0.05). <b>B</b>) PMN infiltration (filled circles) in Peyer’s patches of C57BL/6 mice at various time intervals post infection with avirulent <i>Salmonella aroA asd</i>. Means and standard deviations are shown for groups of three to four mice. No colony-forming units were recovered from day one post infection consistent with rapid in vivo lysis of this cell wall-deficient strain. Similar data were obtained in an independent experiment. <b>C</b>) Colonization levels of attenuated <i>Salmonella aroA</i> (open triangles) and PMN infiltration (filled circles) in Peyer’s patches at various time intervals post infection in BALB/c mice. Means and standard errors are shown for groups of six to eight mice from two independent experiments.</p
Additional file 8: Figure S6. of Combining Shigella Tn-seq data with gold-standard E. coli gene deletion data suggests rare transitions between essential and non-essential gene functionality
No full textThe region of the genome containing the rfb operon is largely uninterrupted by transposon insertions. rfbI, rfc, rfbG, and rfbF are completely uninterrupted by transposon insertions; rfbE, rfbA, and rfbC each harbour only a single transposon insertion. None of these genes except rfbA have orthologous counterparts in E. coli K12 due to a lateral transfer event that occurred at this locus (see main text). This operon encodes genes active in O-antigen biosynthesis. Genes inferred as being essential in Shigella but for which the orthologous deletion genotypes exhibit robust growth in E. coli are indicated in blue. (PDF 177 kb
Additional file 10: Table S2. of Combining Shigella Tn-seq data with gold-standard E. coli gene deletion data suggests rare transitions between essential and non-essential gene functionality
No full textList of chromosomal SNPs and indels observed in the Shigella strain used here that differ from the GenBank sequence NC004741. (TXT 4 kb
<i>Salmonella</i> infection induces intestinal inflammation.
No full text<p><b>A</b>) Polymorphonuclear neutrophils (PMN, magenta) accumulate close to <i>Salmonella</i> (yellow) in the dome area of murine Peyer’s patches 3 h or 48 h after intragastric infection. The scale bar represents 100 µm. Peyer’s patches of naïve mice contained only few neutrophils (data not shown). <b>B</b>) Phenotype of infiltrating CD11b<sup>+</sup> host cells 3 h post infection. The majority of cells represent PMN’s (Ly-6G<sup>hi</sup> Ly-6C<sup>mo</sup>), some other cells represent mobile monocytes (Ly-6G<sup>lo</sup> Ly-6C<sup>hi</sup>). <b>C</b>) Colonization levels of <i>Salmonella</i> (open triangles) and PMN infiltration (filled circles) in Peyer’s patches at various time intervals post infection (d.t., detection threshold for plating). The data might overestimate actual bacterial tissue loads due to potential contamination with residual luminal <i>Salmonella</i> especially at early time points after oral administration. Means and standard deviations are shown for groups of three to four mice. Similar data were obtained in two independent experiments. <b>D</b>) PMN infiltration 3 h post infection in wildtype C57BL/6 mice (B6) and mutant mice with various defects in innate immunity (filled circles). Data for sham-infected B6 are also shown (open circles). Significance of differences to infected B6 was determined using t-test on log-transformed data (**, <i>P</i><0.01; *, <i>P</i><0.05; n.s., <i>P</i>>0.05). Similar data were obtained in three independent experiments.</p
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