Ontology highlight
ABSTRACT:
PROVIDER: PRJEB29407 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR2861340_1.fastq.gz | Fastqsanger.gz | |||
| ERR2861340_2.fastq.gz | Fastqsanger.gz | |||
| ERR2861337_1.fastq.gz | Fastqsanger.gz | |||
| ERR2861337_2.fastq.gz | Fastqsanger.gz | |||
| ERR2861338_1.fastq.gz | Fastqsanger.gz |
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Project description:The emergence of multidrug resistant (MDR) Mycobacterium tuberculosis (Mtb) strains, resistant to the frontline anti-tubercular drugs rifampicin and isoniazid, forces treatment with less effective and toxic second-line drugs and stands to derail TB control efforts. However, the immune response to MDR Mtb infection remains poorly understood. Here, we determined the RNA transcriptional profile of in vitro generated macrophages to infection with either drug susceptible Mtb HN878 or MDR Mtb W_7642 infection.
2018-12-26 | GSE115495 | GEO
Project description:The emergence of drug resistance among tuberculosis (TB) patients is often associated with their non-compliance to the length of the chemotherapy, which can reach up to 2 years for the treatment of multi-drug-resistant (MDR) TB. Drugs that would kill TB faster and would not lead to the development of drug resistance could shorten chemotherapy significantly. In Escherichia coli, the common mechanism of cell death by bactericidal antibiotics is the generation of highly reactive hydroxyl radicals via the Fenton reaction. Since ascorbic acid (vitamin C) is known to drive the Fenton reaction, we tested whether the Fenton reaction could lead to a bactericidal event in Mycobacterium tuberculosis by treating M. tuberculosis cultures with vitamin C. Here, we report that the addition of vitamin C to drug-susceptible, MDR and extensively drug-resistant (XDR) M. tuberculosis strains results in sterilization of the cultures in vitro. We show that the sterilizing effect of vitamin C on M. tuberculosis was dependent on the production of high ferrous ion levels and reactive oxygen species. Although, this potent sterilizing activity of vitamin C against M. tuberculosis in vitro was not observed in mice, we believe this activity needs further investigation. Comparison of vitamin C treated Mycobacterium tuberculosis transcriptome relative to untreated; Three biological replicates, second is a dye flip
2013-05-24 | E-GEOD-42293 | biostudies-arrayexpress
Project description:Among the multidrug-resistant (MDR) clones of Mycobacterium tuberculosis (Mtb) that were epidemiologically particularly successful, the 100-32 MDR Beijing clone, also called B0/W148 clone, has emerged since the early sixties. These B0/W148 strains belonging to the lineage 2 within the global Mtb phylogeny, are the main contributors to the MDR epidemic in Russia and Eastern Europe, and since the USSR’s fall, have also propagated to Western Europe. Among the various mutations that were identified as being specific for the MDR B0/W148 clone, we focused on two found in the transcriptional regulators KdpDE and WhiB6 and characterized in a H37Rv strain background the transcriptional profile associated with these mutations and their potential impact on the in vitro and in vivo growth characteristics.
2024-09-25 | GSE269918 | GEO
Project description:Among the multidrug-resistant (MDR) clones of Mycobacterium tuberculosis (Mtb) that were epidemiologically particularly successful, the 100-32 MDR Beijing clone, also called B0/W148 clone, has emerged since the early sixties. These B0/W148 strains belonging to the lineage 2 within the global Mtb phylogeny, are the main contributors to the MDR epidemic in Russia and Eastern Europe, and since the USSR’s fall, have also propagated to Western Europe. Among the various mutations that were identified as being specific for the MDR B0/W148 clone, we focused on two found in the transcriptional regulators KdpDE and WhiB6 and characterized in a H37Rv strain background the transcriptional profile associated with these mutations and their potential impact on the in vitro and in vivo growth characteristics.
2024-09-25 | GSE269917 | GEO
Project description:Efforts to eradicate TB are largely threatened by drug-resistant tuberculosis, particularly, multidrug-resistant tuberculosis (MDR-TB). It is imperative to find one or more specific biomarkers for diagnosing MDR-TB earlier and declining the incidence. Growing evidences have showed lncRNAs are widely expressed and take part in the genesis and development of many diseases, including tuberculosis. Therefore, to screen the differential lncRNAs among MDR-TB, drug-sensitive tuberculosis(DS-TB) and healthy controls(HCs) is a good strategy to acquire potential biomarkers for MDR-TB diagnosis and partly describe the mechanism of MDR-TB. Here, the present study aimed to investigate the differential expression profile of lncRNAs in serum among patients with MDR-TB ,DS-TB and HCs using lncRNA microarray
2021-09-10 | GSE183787 | GEO
Project description:The emergence of drug resistance among tuberculosis (TB) patients is often associated with their non-compliance to the length of the chemotherapy, which can reach up to 2 years for the treatment of multi-drug-resistant (MDR) TB. Drugs that would kill TB faster and would not lead to the development of drug resistance could shorten chemotherapy significantly. In Escherichia coli, the common mechanism of cell death by bactericidal antibiotics is the generation of highly reactive hydroxyl radicals via the Fenton reaction. Since ascorbic acid (vitamin C) is known to drive the Fenton reaction, we tested whether the Fenton reaction could lead to a bactericidal event in Mycobacterium tuberculosis by treating M. tuberculosis cultures with vitamin C. Here, we report that the addition of vitamin C to drug-susceptible, MDR and extensively drug-resistant (XDR) M. tuberculosis strains results in sterilization of the cultures in vitro. We show that the sterilizing effect of vitamin C on M. tuberculosis was dependent on the production of high ferrous ion levels and reactive oxygen species. Although, this potent sterilizing activity of vitamin C against M. tuberculosis in vitro was not observed in mice, we believe this activity needs further investigation.
2013-05-24 | GSE42293 | GEO
Project description:Rifampicin plays an important role during tuberculosis treatment, which historically contributed for shortening therapy; however, rifampicin resistance has been the intersection for the definition of multi (MDR-TB) and extensively (XDR-TB) resistant outcomes. A key aspect which has contributed for investigations of drug action/resistance is the understanding of the dynamic genome expression, as that analyzed by Proteomics. Proteins from the reference strain, Mycobacterium tuberculosis H37Rv were extracted after 12, 24 and 48 hours over rifampicin challenge at the minimal inhibitory concentration (0.03 μg•mL-1) and identified by LC-MS.
2021-05-04 | PXD014177 | Pride
Project description:Jamshidi2007 - Genome-scale metabolic network
of Mycobacterium tuberculosis (iNJ661)
This model is described in the article:
Investigating the metabolic
capabilities of Mycobacterium tuberculosis H37Rv using the in
silico strain iNJ661 and proposing alternative drug
targets.
Jamshidi N, Palsson BØ.
BMC Syst Biol 2007; 1: 26
Abstract:
BACKGROUND: Mycobacterium tuberculosis continues to be a
major pathogen in the third world, killing almost 2 million
people a year by the most recent estimates. Even in
industrialized countries, the emergence of multi-drug resistant
(MDR) strains of tuberculosis hails the need to develop
additional medications for treatment. Many of the drugs used
for treatment of tuberculosis target metabolic enzymes.
Genome-scale models can be used for analysis, discovery, and as
hypothesis generating tools, which will hopefully assist the
rational drug development process. These models need to be able
to assimilate data from large datasets and analyze them.
RESULTS: We completed a bottom up reconstruction of the
metabolic network of Mycobacterium tuberculosis H37Rv. This
functional in silico bacterium, iNJ661, contains 661 genes and
939 reactions and can produce many of the complex compounds
characteristic to tuberculosis, such as mycolic acids and
mycocerosates. We grew this bacterium in silico on various
media, analyzed the model in the context of multiple
high-throughput data sets, and finally we analyzed the network
in an 'unbiased' manner by calculating the Hard Coupled
Reaction (HCR) sets, groups of reactions that are forced to
operate in unison due to mass conservation and connectivity
constraints. CONCLUSION: Although we observed growth rates
comparable to experimental observations (doubling times ranging
from about 12 to 24 hours) in different media, comparisons of
gene essentiality with experimental data were less encouraging
(generally about 55%). The reasons for the often conflicting
results were multi-fold, including gene expression variability
under different conditions and lack of complete biological
knowledge. Some of the inconsistencies between in vitro and in
silico or in vivo and in silico results highlight specific loci
that are worth further experimental investigations. Finally, by
considering the HCR sets in the context of known drug targets
for tuberculosis treatment we proposed new alternative, but
equivalent drug targets.
This model is hosted on
BioModels Database
and identified by:
MODEL1507180001.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2024-10-15 | MODEL1507180001 | BioModels
Project description:During Tuberculosis, Mycobacterium uses host macrophage cholesterol as a carbon and energy source. To mimic these conditions Mycobacterium smegmatis cultured in minimal medium (MM) has been used to induce cholesterol consumption in vitro. During cultivation, M. smegmatis con-sumes MM cholesterol and changes the accumulation of the cell wall compounds such as PIMs, LM and LAM, which plays an important role in its pathogenicity. These changes led to cell sur-face hydrophobicity modifications and H2O2 susceptibility. Furthermore, when M. smegmatis in-fects J774A.1 macrophages it induces granuloma-like structures formation. The present study aims to access macrophage molecular disturbances caused by M. smegmatis after cholesterol con-sumption through proteomics analyses.
2022-02-17 | PXD025783 | Pride
Project description:Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), latently infects one quarter of the world’s population. The rise of multidrug resistant (MDR) Mtb infections worldwide presents a significant obstacle to curb TB globally. While human studies report dysregulated immune responses in MDR TB patients, there is a lack of clear understanding of the host-pathogen interactions following MDR Mtb infection. We recently showed that Mtb carrying a rifampicin drug resistance (RDR)-conferring single nucleotide polymorphism in the RNA polymerase-B gene (Mtb rpoB-H445Y) can modulate host macrophage metabolic reprogramming by production of Type I IFNs. Here, using a mouse model, we have characterized the host immune response in vivo following RDR Mtb infection. We show that despite establishment of Mtb infection in the lung and dissemination to the peripheral organs, lung myeloid and lymphoid immune responses to RDR Mtb is suppressed through a Type I IFN-dependent mechanism. These results coincide with a muted responses in the bone marrow hematopoietic stem and progenitor cells (HSPCs) and progenitors following RDR Mtb infection. These results suggest that host directed therapeutics and vaccines for drug resistant TB may need to be target specific host immune pathways for protection.
2022-06-01 | GSE176423 | GEO