Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR3257980_1.fastq.gz | Fastqsanger.gz | |||
| ERR3257980_2.fastq.gz | Fastqsanger.gz | |||
| ERR3257990_1.fastq.gz | Fastqsanger.gz | |||
| ERR3257990_2.fastq.gz | Fastqsanger.gz | |||
| ERR3258000_1.fastq.gz | Fastqsanger.gz |
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Project description:Tuberculosis (TB) remains a deadly disease. The genetic diversity of Mycobacterium tuberculosis was neglected in the past, but is increasingly recognized as a determinant of immune responses and clinical outcomes of TB. However, how this bacterial diversity orchestrates immune responses to direct differences in TB severity remains unknown. We studied 681 patients with pulmonary TB and found that phylogenetically related M. tuberculosis isolates from cases with mild disease induced robust cytokine responses in macrophages. In contrast, isolates associated with severe TB cases failed to do so. Using representative isolates, we show that M. tuberculosis inducing a low cytokine response in macrophages also diminished activation of cytosolic surveillance systems, including cGAS and the inflammasome, suggesting a novel mechanism of immune escape. Isolates exhibiting this evasion strategy carried mutations in various components of the ESX-I secretion system. We conclude that host interactions with different M. tuberculosis strains results in variable TB severity.
2020-02-26 | GSE138580 | GEO
Project description:Oxadiazolone (OX) derivatives have been investigated for their antimycobacterial activity against three pathogenic slow-growing mycobacteria: Mycobacterium marinum, Mycobacterium bovis BCG and the avirulent Mycobacterium tuberculosis (M. tb) mc26230. The encouraging MIC values obtained prompted us to test them against virulent M. tb H37Rv growth either in broth medium or inside macrophages. The OX compounds displayed a diversity of action and were found to act either on extracellular M. tb growth only with moderated MIC, or both intracellularly on infected macrophages as well as extracellularly on bacterial growth. One OX derivatives, HPOX, was selected and used in a competitive labelling/enrichment assay against the activity-based probe Desthiobiotin-FP in order to identify its putative target(s). This approach, combined with mass spectrometry, identified 18 potential candidates, all being serine or cysteine enzymes involved in M. tb lipid metabolism and/or in cell wall biosynthesis. Among them, Ag85A, CaeA, TesA, KasA and MetA have been reported as essential for in vitro growth of M. tb and/or its survival and persistence inside macrophages. Overall, our findings support the assumption that OX derivatives may represent a novel class of multi-target inhibitors leading to the arrest of M. tb growth through a cumulative inhibition of a large number of Ser- and Cys-containing enzymes involved in various important physiological processes.
2018-09-25 | PXD010255 | Pride
Project description:Even though recent reports estimate a reduction in the spread and contraction of Tuberculosis (TB), 30 % of the world population are currently being latently infected by Mycobacterium tuberculosis (Mtb). This latent infection can at any time develop into active disease. Biomarkers to monitor this process as well as biomarkers for disease susceptibility and TB diagnosis is urgently needed in order to facilitate a more drastic decrease in the spread of Mtb and better care for TB patients. Our understanding of biology combined with evolving technical advances in high-throughput techniques, led us to investigate the possibility of additional role players (epigenetics and proteomics) in the quest to (a) understand the biology of TB host response and (b) search for biomarkers in TB diagnostics and –susceptibility. We engaged in a pilot study, using a relatively small sample set to interrogate the DNA methylome, transcriptome and proteome in monocytes and granulocytes of TB patients and healthy latently infected participants. The observations in this study provide a first glimpse at the level- and sources of diversity in the epigenome and proteome amongst TB patients and latently infected controls despite limitations due to small sample size. Functionally the differences between the disease phenotypes observed in the different platforms were congruent and suggest regulation of function not only at the transcriptional level, but also by DNA methylation and microRNA. We conclude that the current data support the notion to develop a large scale study of especially the DNA methylome while care should be taken in the study design to account for variation based on gender, age and cell type.
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Project description:We used single cell RNA sequencing (scRNA-seq) to analyze the diversity transcriptomic profiles micro-surgically dissected metastatic regions of the sentinel lymphonodes (3 different condition)
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Project description:Monocyte miRNAs govern both protective and pathological responses during tuberculosis through their differential expression and emerged as potent target for biomarker discovery and host-directed therapeutics. Thus, our profound interest is to look at the miRNA profile of sorted monocytes across TB disease spectrum (drug-resistance TB (DR-TB), drug-sensitive TB (DS-TB) and latent TB) and healthy individuals (HC) to understand the underlying pathophysiology and their regulatory mechanism.
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Project description:To evaluate whether TB infections are associated with any lncRNA signatures in humans, we therefore used human lncRNAs microarray and hierarchical clustering analyses to compare lncRNAs expression in active TB patients and healthy controls. From 15,683 denoted lncRNAs, 5076 lncRNAs were identified to be differentially expressed (TB/HC > 2 or TB/HC< 0.5) in peripheral blood mononuclear cells (PBMCs) between TB and healthy subjects.
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Project description:Coculturing experiments involving three microbial species: Aspergillus (A), Trichoderma (T), and Bacillus (B), representing fungi (A, T) and bacteria (B), respectively. These experiments encompassed various interaction levels, including dual cultures (AB, AT, TB) and triple cultures (ATB). Metabolic profiling by LC-QTOFMS revealed the effect of interaction level on the productivity and diversity of microbial specialized metabolites.
2024-06-05 | MSV000094943 | MassIVE
Project description:Tuberculosis (TB) is one of the deadliest infectious disorders in the world. To effectively TB manage, an essential step is to gain insight into the lineage of Mycobacterium tuberculosis (MTB) strains and the distribution of drug resistance. Although the Campania region is declared a cluster area for the infection, to contribute to the effort to understand TB evolution and transmission, still poorly known, we have generated a dataset of 159 genomes of MTB strains, from Campania region collected during 2018-2021, obtained from the analysis of whole genome sequence data. The results show that the most frequent MTB lineage is the 4 according for 129 strains (81.11%). Regarding drug resistance, 139 strains (87.4%) were classified as multi susceptible, while the remaining 20 (12.58%) showed drug resistance. Among the drug-resistance strains, 8 were isoniazid-resistant MTB (HR-MTB), 7 were resistant only to one antibiotic (3 were resistant only to ethambutol and 3 isolate to streptomycin while one isolate showed resistance to fluoroquinolones), 4 multidrug-resistant MTB, while only one was classified as pre-extensively drug-resistant MTB (pre-XDR). This dataset expands the existing available knowledge on drug resistance and evolution of MTB, contributing to further TB-related genomics studies to improve the management of TB infection.
2023-11-17 | E-MTAB-13058 | biostudies-arrayexpress
Project description:Mycobacterium tuberculosis infects two billion people across the globe, and results in 8-9 million new tuberculosis (TB) cases and 1-1.5 million deaths each year. Most patients have no known genetic basis that predisposes them to disease. Here, we investigate the complex genetic basis of pulmonary TB by modelling human genetic diversity with the Diversity Outbred mouse population. When infected with M. tuberculosis, one-third develop early onset, rapidly progressive, necrotizing granulomas and succumb within 60 days. The remaining develop non-necrotizing granulomas and survive longer than 60 days. Genetic mapping using immune and inflammatory mediators; and clinical, microbiological, and granuloma correlates of disease identified five new loci on mouse chromosomes 1, 2, 4, 16; and three known loci on chromosomes 3 and 17. Further, multiple positively correlated traits shared loci on chromosomes 1, 16, and 17 and had similar patterns of allele effects, suggesting these loci contain critical genetic regulators of inflammatory responses to M. tuberculosis. To narrow the list of candidate genes, we used a machine learning strategy that integrated gene expression signatures from lungs of M. tuberculosis-infected Diversity Outbred mice with gene interaction networks to generate scores representing functional relationships. The scores were used to rank candidates for each mapped trait, resulting in 11 candidate genes: Ncf2, Fam20b, S100a8, S100a9, Itgb5, Fstl1, Zbtb20, Ddr1, Ier3, Vegfa, and Zfp318. Although all candidates have roles in infection, inflammation, cell migration, extracellular matrix remodeling, or intracellular signaling, and all contain single nucleotide polymorphisms (SNPs), SNPs in only four genes (S100a8, Itgb5, Fstl1, Zfp318) are predicted to have deleterious effects on protein functions. We performed methodological and candidate validations to (i) assess biological relevance of predicted allele effects by showing that Diversity Outbred mice carrying PWH/PhJ alleles at the H-2 locus on chromosome 17 QTL have shorter survival; (ii) confirm accuracy of predicted allele effects by quantifying S100A8 protein in inbred founder strains; and (iii) infection of C57BL/6 mice deficient for the S100a8 gene. Overall, this body of work demonstrates that systems genetics using Diversity Outbred mice can identify new (and known) QTLs and functionally relevant gene candidates that may be major regulators of complex host-pathogens interactions contributing to granuloma necrosis and acute inflammation in pulmonary TB.
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