Whole-genome sequences and comparative genomics of Salmonella enterica serovar Typhi isolates from patients in China.
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REPOSITORIES: ENA
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Project description:Human genetic diversity can reveal critical factors in host-pathogen interactions. This is especially useful for human-restricted pathogens like Salmonella enterica serovar Typhi (S. Typhi), the cause of Typhoid fever. One key dynamic during infection is competition for nutrients: host cells attempt to restrict intracellular replication by depriving bacteria of key nutrients or delivering toxic metabolites in a process called nutritional immunity. Here, a cellular genome-wide association study of intracellular replication by S. Typhi in nearly a thousand cell lines from around the world—and extensive follow-up using intracellular S. Typhi transcriptomics and manipulation of magnesium concentrations—demonstrates that the divalent cation channel mucolipin-2 (MCOLN2) restricts S. Typhi intracellular replication through magnesium deprivation. Our results reveal natural diversity in Mg2+ limitation as a key component of nutritional immunity against S. Typhi.
2023-01-05 | GSE222194 | GEO
Project description:Salmonella enterica subsp. enterica contains more than 2,600 serovars of which four are of major medical relevance for humans. While the typhoidal serovars (Typhi and Paratyphi A) are human-restricted and cause enteric fever, non-typhoidal Salmonella serovars (Typhimurium and Enteritidis) have a broad host range and predominantly cause gastroenteritis. In this study, we compared the core proteomes of Salmonella Typhi, Paratyphi A, Typhimurium and Enteritidis using contemporary proteomics. Five isolates, covering different geographical origins, and one reference strain per serovar were grown in vitro to the exponential phase. Protein levels of orthologous proteins between serovars were compared and subjected to gene ontology term enrichment and inferred regulatory interactions. Differential expression of the core proteomes of the typhoidal serovars appears mainly related to cell surface components and, for the non-typhoidal serovars, to pathogenicity. Our findings may guide future development of novel diagnostics and vaccines, and understanding of disease progression.
2019-05-13 | PXD011154 | Pride
Project description:Macrophages provide a crucial environment for Salmonella enterica serovar Typhi (S. Typhi) to multiply during typhoid fever, yet our understanding of how human macrophages and S. Typhi interact remains limited. In this study, we delve into the dynamics of S. Typhi replication within human macrophages and the resulting heterogeneous transcriptomic responses of macrophages during infection. Our study reveals key factors that influence macrophage diversity, uncovering distinct immune and metabolic pathways associated with different stages of S. Typhi intracellular replication in macrophages. Of note, we found that macrophages harboring replicating S. Typhi are skewed towards an M1 pro-inflammatory state, whereas macrophages containing non-replicating S. Typhi exhibit neither a distinct M1 pro-inflammatory nor M2 anti-inflammatory state. Additionally, macrophages with replicating S. Typhi were characterized by the increased expression of genes associated with STAT3 phosphorylation and the activation of the STAT3 transcription factor. Our results shed light on transcriptomic pathways involved in the susceptibility of human macrophages to intracellular S. Typhi replication, thereby providing crucial insight into host phenotypes that restrict and support S. Typhi infection.
2024-05-20 | GSE267899 | GEO
Project description:Transcriptional profiling of three sequenced S. enterica strains: S. Typhimurium LT2, S. Typhi CT18, and S. Typhi Ty2 in PhoP-inducing and non-inducing conditions in vitro, and compared these results to profiles of phoP-/Q- mutants derived from S. Typhimurium LT2 and S. Typhi Ty2.
2009-08-19 | GSE17670 | GEO
Project description:Salmonella enterica serovar Typhi (S. Typhi), a human-restricted pathogen, enters the host through the gut to cause typhoid fever. Recent calculations of the typhoid fever burden estimated that more than 20 million new typhoid fever cases occur in low and middle-income countries, resulting in 129,000-223,000 deaths yearly. Interestingly, upon the resolution of acute disease, 1%-5% of patients become asymptomatic chronic carriers of S. Typhi. Chronically infected hosts are not only critical reservoirs of infection that transmit the disease to naive individuals but are also predisposed to developing gallbladder carcinoma (GBC). Nevertheless, the molecular mechanisms involved in the early interactions between gallbladder epithelial cells and S. Typhi remain largely unknown. Based on our previous studies showing that very closely related S. Typhi strains elicit distinct innate immune responses, we hypothesized that host molecular pathways activated by S. Typhi strains derived from acutely and chronically infected patients will differ. To test this hypothesis, we used a novel human organoid-derived polarized gallbladder monolayer (HODGM) model, and 13 S. Typhi strains derived from acutely (n=6) and chronically (n=7) infected patients. We found that S. Typhi strains derived from acutely and chronically infected patients differentially regulate mitogen-activated protein kinase (MAPK) and S6 transcription factors. This differential regulation impacts, at least in part, the cytokine signaling pathway involved in the production of TNF- and IL-6 and is likely to play a critical role in inducing chronic S. Typhi infection in the gallbladder.
2024-04-05 | GSE253700 | GEO
Project description:Transcriptional profiling of three sequenced S. enterica strains: S. Typhimurium LT2, S. Typhi CT18, and S. Typhi Ty2 in PhoP-inducing and non-inducing conditions in vitro, and compared these results to profiles of phoP-/Q- mutants derived from S. Typhimurium LT2 and S. Typhi Ty2. Two-condition experiment: Each strain above was grown in PhoP-inducing (Low Magnesium concentration) and PhoP non-inducing conditions (High Magnesium concentration) with 1 dye reversal.
2010-05-06 | E-GEOD-17670 | biostudies-arrayexpress
Project description:<p>Vaccine development against <i>Salmonella enterica</i> serovar Typhi (<i>S</i>. Typhi) requires a better understanding of interaction between human host and the resident microbial consortia in gastrointestinal tract. Healthy adult volunteers received either Ty21a, M01ZH09 or placebo, and underwent challenges with wt <i>S</i>. Typhi. Stool samples were collected at the screening interview (Baseline 1), prior to the first vaccination visit (Baseline 2), during vaccination (Day -28 and -26 for placebo and M01ZH09 groups; Day -32, -30, -28, -26 for Ty21a group), prior to challenge with <i>S</i>. Typhi (Day 0), and after challenge (day 0 12h, day 1, day 3, day 7, and day 10). 16S rRNA and messenger RNA were extracted from stool and sequenced on the Illumina Miseq and HiSeq 2000 platforms, respectively.</p>
| phs001521 | dbGaP
Project description:Transcriptional profiling of mycobacterium tuberculosis clinical isolates in China comparing extensively drug-resistant tuberculosis with drug sensitive one.
2009-04-04 | GSE15540 | GEO
Project description:S. Typhi was cultured in broth, diluted and resuspended in water. RNA was prepared from the original broth culture (control), and from S. Typhi suspended in water for 0.5, 6 and 24 hours incubated at 28c without shaking
2018-09-07 | E-MTAB-7160 | biostudies-arrayexpress
Project description:Six sequencing libraries was prepared from S. Typhi planktonic cells and biofilm cells using Illumina HiSeq 2500 sequencing to investigate differential gene expression between the two conditions. The transcriptome was processed using Cufflinks and there were a total of 35 up-regulated genes and 29 down-regulated genes log2-fold change values of greater than 2 and less than negative 2. The differentially expressed genes were identified using BLAST and the functions was analysed. This study provides an overview of the genes that are differentially expressed in S. Typhi when it transitions from the planktonic to the biofilm phenotype. The data will provide a basis for further study is necessary to uncover the mechanisms of biofilm formation in S. Typhi and discovery of novel gene functions or pathways associated with the development of the typhoid carrier state. This data may also be used to elucidate the effect of biofilm on the virulence and pathogenicity of S. Typhi in chronic carriers.
2017-10-31 | GSE93686 | GEO