Genomic analysis of S. Paratyphi A
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ABSTRACT:
PROVIDER: PRJEB44794 | ENA |
REPOSITORIES: ENA
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Project description:This studies describes the transcriptional response in whole blood derived from healthy adult volunteers experimentally infected with S. Paratyphi A. Samples were collected at pre-challenge baseline (Group: CTRL), at day 7 after challenge in those participants who stayed well over 14 days following challenge (Group: suspected Enteric Fever - sEF). Participants who developed signs of enteric fever were sampled at the time of inititiation of antibiotics (Group: EF).In this group diagnosis was confirmed by blood culture positive for S. Paratyphi (SPT). Antibiotic therapy commenced at time of diagnosis or at day 14 after challenge in those who did not develop symptoms. The clinical results of this study have been published in: Dobinson et al. Evaluation of the Clinical and Microbiological Response to Salmonella Paratyphi A Infection in the First Paratyphoid Human Challenge Model. Clin Infect Dis. 2017 Apr 15;64(8):1066-1073.
2019-09-02 | GSE114033 | 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:In this study, whole blood samples were used to determine the gene expression of febrile culture confirmed enteric fever cases (ST = S. Typhi; SPT = S. Paratyphi), febrile culture negative individuals presenting to hospital in Kathamandu (sEF = suspected enteric fever), and healthy community controls (CTRL).
2019-09-02 | GSE113866 | GEO
Project description:Comparative genomic analysis of a temporally and locally diverse set of S. enterica ssp I sv Paratyphi A isolates Keywords: ordered
2004-07-21 | GSE1500 | GEO
Project description:Surveillance of Enteric Fever in India (SEFI)
| PRJEB36270 | ENA
Project description:Background: Salmonella Typhi and Salmonella Paratyphi A are the agents of enteric (typhoid) fever; both can establish chronic carriage in the gallbladder. Chronic Salmonella carriers are typically asymptomatic, intermittently shedding bacteria in the feces, and contributing to disease transmission. Detecting chronic carriers is of public health relevance in areas where enteric fever is endemic, but there are no routinely used methods for prospectively identifying those carrying Salmonella in their gallbladder. Methodology/Principal Findings: Here we aimed to identify biomarkers of Salmonella carriage using metabolite profiling. We performed metabolite profiling on plasma from Nepali patients undergoing cholecystectomy with confirmed S. Typhi or S. Paratyphi A gallbladder carriage (and non-carriage controls) using two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GCxGC-TOFMS) and supervised pattern recognition modeling. We were able to significantly discriminate Salmonella carriage samples from non-carriage control samples. We were also able to detect differential signatures between S. Typhi and S. Paratyphi A carriers. We additionally compared carriage metabolite profiles with profiles generated during acute infection; these data revealed substantial heterogeneity between metabolites associated with acute enteric fever and chronic carriage. Lastly, we found that Salmonella carriers could be significantly distinguished from non-carriage controls using only five metabolites, indicating the potential of these metabolites as diagnostic markers for detecting chronic Salmonella carriers. Conclusions/Significance: Our novel approach has highlighted the potential of using metabolomics to search for diagnostic markers of chronic Salmonella carriage. We suggest further epidemiological investigations of these potential biomarkers in alternative endemic enteric fever settings.
2018-01-17 | MTBLS579 | MetaboLights
Project description:Comparative genomic analysis of a temporally and locally diverse set of S. enterica ssp I sv Paratyphi A isolates Keywords: ordered
2004-07-21 | E-GEOD-1500 | biostudies-arrayexpress
Project description:In this work, we applied an RNA analysis method, Selective Capture of Transcribed Sequences (SCOTS), and cDNA hybridization-microarray technology to identify S. Paratyphi A transcripts expressed by bacteria in the blood of three patients in Bangladesh. In total, we detected 1798 S. Paratyphi A mRNAs expressed in the blood of infected humans (43.9% of the ORFeome). Of these, we identified 868 in at least two patients, and 315 in all three patients. S. Paratyphi A transcripts identified in at least two patients encode proteins involved in energy metabolism, nutrient and iron acquisition, vitamin biosynthesis, stress responses, oxidative stress resistance, and pathogenesis. A number of detected transcripts are expressed from PhoP and SlyA-regulated genes associated with intra-macrophage survival, genes contained within Salmonella Pathogenicity Islands (SPIs) 1-4, 6, 10, 13, and 16, as well as RpoS-regulated genes. The largest category of identified transcripts are those encoding proteins with unknown function. When comparing level of bacterial mRNA detection using in vivo samples collected from infected patients to samples from in vitro grown organisms, we found significant differences for 347, 391, and 456 S. Paratyphi A transcripts in each of three individual patients (approximately 9.7% of the ORFeome). Of these, expression of 194 transcripts (4.7% of ORFs) was concordant in two or more patients, and 41 in all patients. Genes encoding these transcripts are contained within SPI-1, 3, 6 and 10, are PhoP-regulated genes, are involved in energy metabolism, nutrient acquisition, drug resistance, or are uncharacterized genes. Using quantitative RT-PCR, we confirmed increased gene expression in vivo for a subset of genes identified in our analyses. We compared transcriptional profiles of S. Paratyphi A from the blood of infected humans to S. Paratyphi A grown in vitro. Replicates and dye-swaps were performed.
2010-09-06 | E-GEOD-22958 | biostudies-arrayexpress
Project description:Salmonella enterica is comprised of genetically distinct “serovars”, that together provide an intriguing model for exploring the genetic basis of pathogen evolution. While the genomes of numerous Salmonella isolates with broad variations in host range and human disease manifestations have been sequenced, the functional links between genetic and phenotypic differences among these serovars remain poorly understood. Here, we conduct high-throughput functional genomics on both generalist (Typhimurium) and human-restricted (Typhi & Paratyphi A) Salmonella at unprecedented scale in the study of this enteric pathogen. Using a comprehensive systems biology approach, we identify gene networks with serovar-specific fitness effects across 25 host-associated stresses encountered at key stages of human infection. By experimentally perturbing these networks, we characterize previously undescribed pseudogenes in human-adapted Salmonella. Overall, this work highlights specific vulnerabilities encoded within human-restricted Salmonella that are linked to the degradation of their genomes, shedding light into the evolution of this enteric pathogen.
2024-04-12 | GSE262769 | GEO
Project description:Here, we report an ssDNA aptamer with high specificity and affinity towards Salmonella paratyphi A generated using the whole-cell SELEX process. The aptamers generated against an organism show salient features, such as higher affinity than existing antibodies, and are highly specific towards the targeted organism. Thus, the generated aptamer sequences can serve as potential biomarkers for the onsite detection of pathogens with high specificity and sensitivity. Molecular dynamics simulation was used to model the linear chain of the aptamers to a three-dimensional conformation, and the binding mechanism against DNA gyrase was established.
2019-12-31 | GSE137006 | GEO