Ontology highlight
ABSTRACT:
PROVIDER: PRJNA597713 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10767000_1.fastq.gz | Fastqsanger.gz | |||
| SRR10767000_2.fastq.gz | Fastqsanger.gz | |||
| SRR10767001_1.fastq.gz | Fastqsanger.gz | |||
| SRR10767001_2.fastq.gz | Fastqsanger.gz | |||
| SRR10767002_1.fastq.gz | Fastqsanger.gz |
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Project description:EXIT-RIF: Evaluating the Xpert Impact on Tuberculosis – RIFampicin Resistance
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Project description:A cell-based phenotypic screen for inhibitors of biofilm formation in Mycobacterium tuberculosis (Mtb) identified the small molecule TCA1, which has bactericidal activity against both drug susceptible and drug resistant Mtb, and synergizes with rifampicin (RIF) or isoniazid (INH) in sterilization of Mtb in vitro. In addition, TCA1 has bactericidal activity against non-replicating Mtb in vitro and is efficacious in acute and chronic Mtb infection mouse models, both alone and in combination with INH or RIF. Transcriptional analysis revealed that TCA1 down-regulates genes known to be involved in Mtb dormancy and drug tolerance. Mutagenesis and affinity-based methods identified DprE1 and MoeW, enzymes involved in cell wall and molybdenum cofactor biosynthesis, respectively, as the targets responsible for TCA1M-bM-^@M-^Ys activity. These in vitro and in vivo results indicate that TCA1functions by a novel mechanism and suggest that it may be the first product of a promising new approach for the development of anti-tuberculosis drugs. Transcriptional profile of TCA1-treated cells relative to DMSO-treated control. Three biological replicates, third is a dye flip.
2013-05-24 | E-GEOD-42151 | biostudies-arrayexpress
Project description:A cell-based phenotypic screen for inhibitors of biofilm formation in Mycobacterium tuberculosis (Mtb) identified the small molecule TCA1, which has bactericidal activity against both drug susceptible and drug resistant Mtb, and synergizes with rifampicin (RIF) or isoniazid (INH) in sterilization of Mtb in vitro. In addition, TCA1 has bactericidal activity against non-replicating Mtb in vitro and is efficacious in acute and chronic Mtb infection mouse models, both alone and in combination with INH or RIF. Transcriptional analysis revealed that TCA1 down-regulates genes known to be involved in Mtb dormancy and drug tolerance. Mutagenesis and affinity-based methods identified DprE1 and MoeW, enzymes involved in cell wall and molybdenum cofactor biosynthesis, respectively, as the targets responsible for TCA1’s activity. These in vitro and in vivo results indicate that TCA1functions by a novel mechanism and suggest that it may be the first product of a promising new approach for the development of anti-tuberculosis drugs.
2013-05-24 | GSE42151 | GEO
Project description:To explore the mechanism of drug resistance, most works focused on resistance associated genetic mutations, whereas concerns for resistance related gene expression are relatively low. Here a global expression analysis was performed between a reference strain H37Rv and two clinical extensively drug-resistant (XDR) strains with three anti-TB drug exposures {isoniazid (INH), capreomycin (CAP), rifampicin (RIF)} Strains were grown in Middlebrook 7H9 broth supplemented with ADC, 0.05% Tween 80 and 0.2% glycerol to an OD600 of 0.5-0.6, and then respectively treated with control (water), 10×MIC INH, 1×MIC RIF and CAP for 6hr.
2014-01-07 | E-GEOD-53843 | biostudies-arrayexpress
Project description:To explore the mechanism of drug resistance, most works focused on resistance associated genetic mutations, whereas concerns for resistance related gene expression are relatively low. Here a global expression analysis was performed between a reference strain H37Rv and two clinical extensively drug-resistant (XDR) strains with three anti-TB drug exposures {isoniazid (INH), capreomycin (CAP), rifampicin (RIF)}
2014-01-07 | GSE53843 | GEO
Project description:Background: Tuberculosis (TB) remains a major public health problem, especially in developing countries, with 1.5 million deaths annually worldwide. Antibiotics are commonly used in the treatment of bacterial infections. As with most drugs, antibiotic treatment can also alter host metabolism, leading to adverse side-effects. Antibiotics can also interfere with the immune system, indirectly through the disturbance of the body’s microbiota or directly by modulating the functions of immune cells. It is therefore important to understand how antibiotic treatment modulates immune cell functions. Here we aim to evaluate the impact of first-line anti-TB drugs on the response of human macrophages infected with Mycobacterium tuberculosis (MTB). Results: Human macrophages were stimulated with heat-killed Mycobacterium tuberculosis (hk-MTB) and treated with isoniazid (INH), rifampicin (RIF), ethambutol, pyrazinamide (PZA) or amikacin (AMK). After 24h of treatment, RNA was collected and we characterized the genome-wide gene expression profiles of drug-treated cells by RNAseq. 556, 752 and 7 genes were differentially expressed in hk-MTB-stimulated macrophages upon RIF, PZA and EMB treatment respectively, whereas in uninfected macrophages, 448 and 11 genes were differentially expressed upon RIF and PZA treatment respectively. No genes were differentially expressed upon INH and AMK treatment. We classified all modulated genes by performing gene-set enrichment analysis. The gene set regulated by PZA in infected macrophages was significantly enriched for genes involved in Integral to lumenal side of endoplasmic reticulum membrane, Cytokine-mediated signaling pathway or Interferon-gamma-mediated signaling pathway. In hk-MTB-stimulated macrophages treated by RIF, we found an enrichment in Endoplasmic reticulum unfolded protein response, NADP binding or Lipid metabolic process. Conclusions: Our results highlight the importance to understand how antibiotic treatment modulates macrophage (Mφ) functions, and more generally, how it impacts the host immune response.
2020-04-29 | GSE143731 | GEO
Project description:Blood transcriptional signatures may discriminate individuals with tuberculosis (TB) from disease-free controls, or from patients with other infectious or respiratory diseases. To systematically evaluate the diagnostic accuracy of published transcriptional signatures in a clinically relevant population with high burden of TB and human immunodeficiency virus (HIV), adults presenting for investigation of possible pulmonary TB were consecutively recruited at a TB clinic in South Africa. At enrolment, peripheral blood was collected in Tempus tubes (for RNA sequencing) and patients provided two sputum samples (for Xpert and liquid culture). Amongst 181 patients (median age 35 years), 44 (24%) were infected with human immunodeficiency virus (HIV). 54 patients (30%) were diagnosed with Xpert- or culture-positive TB. No alternate diagnoses were available for Xpert- and culture-negative non-TB patients.
2020-03-17 | E-MTAB-8290 | biostudies-arrayexpress
Project description:Analysis of Mtb strains harboring major RIF-resistance mutations in Hanoi, Vietnam
| PRJDB15583 | ENA