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.
2021-02-10 | GSE125870 | GEO
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), caused by Mycobacterium tuberculosis (Mtb), is defined by granulomas—immune aggregates that either contain or support bacterial replication. Macrophages, fundamental components of these lesions, are crucial to TB pathogenesis, yet their phenotypic and functional diversity remains incompletely understood. Here, we used single-cell RNA sequencing and immunofluorescence to profile macrophages in lung tissue and granulomas from a nonhuman primate model of early TB. We identified transcriptionally distinct subsets, including embryonic-origin tissue-resident alveolar macrophages and monocyte-derived alveolar and interstitial macrophages, each with distinct spatial localization in granulomas. Tissue-resident alveolar macrophages and a subset undergoing epithelial-to-mesenchymal transition accounted for the highest frequency of Mtb-infected cells. Infected cells exhibited differential expression of immune- and migration-associated genes compared to uninfected counterparts, suggesting Mtb either induces or exploits these pathways as a survival strategy. These findings highlight macrophage heterogeneity as a major driver of differential susceptibility to Mtb and provide insights relevant to future immunomodulatory strategies.
2025-11-30 | GSE296788 | GEO
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