Expression profiling of extensively drug-resistant tuberculosis isolates and H37Rv exposed to anti-TB compounds
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ABSTRACT:
ORGANISM(S): Mycobacterium tuberculosis Mycobacterium tuberculosis H37Rv
PROVIDER: GSE53843 | GEO | 2014/01/07
SECONDARY ACCESSION(S): PRJNA233510
REPOSITORIES: GEO
Similar Datasets
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: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:This project provides the first characterization of protein differences in clinical isolates of Mtb after acquisition of resistance to isoniazid (INH), one of the most important drug treatment options against TB. This study determines the global protein differences in a clinical isogenic pair of Mtb, comparing INH susceptibility versus INH resistance.
2016-03-14 | PXD002986 | Pride
Project description:Extensively drug resistant tuberculosis (XDR-TB) showed many different characteristics including the extreme drug resistance versus the drug sensitive clinical isolates (DS-TB), to know better about the reasons we used the tuberculosis host cells named as THP-1 (one kind of the macrophage cells) to be infected by the XDR-TB and DS-TB.DS strain A36 and the XDR strain B42 and was typical and selected by our lab. Then the total RNA of infected or uninfected THP-1 cells was extract and purified for the analysis by the chip (22K Human Genome chip representing the 21522 ORF of human with the oligonucleotide probe of 70 mer from CapitalBio Corp., Beijing, China). The results reflected the different expressed genes involved in apoptosis, secreted cytokines and signal pathway and so on. Those results might indicate the how the XDR-TB cause the pathogenesis.
2009-04-04 | GSE15539 | 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:Background: Understanding how growth state influences Mycobacterium tuberculosis responses to antibiotic exposure provides a window into drug action during patient chemotherapy. In this article, we describe the transcriptional programs mediated by isoniazid (INH) during the transition from log-phase to nonreplicating bacilli, from INH-sensitive to INH-tolerant bacilli respectively, using the Wayne model. Results: INH treatment did not elicit a transcriptional response from nonreplicating bacteria under microarophilic conditions (NRP2), unlike the induction of a robust and well-characterized INH signature in log-phase bacilli. Conclusion: The differential regulation (between drug-free NRP2 and log-phase bacilli) of genes directly implicated in INH resistance could not account for the abrogation of INH killing in nongrowing bacilli. Thus, factors affecting the requirement for mycolic acids and the redox status of bacilli are likely responsible for the reduction in INH efficacy. We speculate on additional mechanisms revealed by transcriptome analysis that might account for INH tolerance. Data is also available from <ahref=http://bugs.sgul.ac.uk/E-BUGS-104 target=_blank>BuG@Sbase</a>
2011-01-17 | E-BUGS-104 | biostudies-arrayexpress
Project description:Bacteria commonly adapt to stresses by altering gene expression. To understand the response of M. tuberculosis (MTB) to various antibacterial agents, we performed transcriptomics on MTB bacilli exposed to several test compounds as well as known drugs (capreomycin, cycloserine, ethionamide, isoniazid, kanamycin, moxifloxacin, PA-824, rifampicin, streptomycin). Bacteria were exposed for 16 hrs to various concentrations of each drug (different multiples of the compound's MIC), as noted in the title of each sample. RNA was isolated and applied to arrays provided by TIGR under the NIAID contract N01-AI-15447
2015-11-11 | E-GEOD-71200 | biostudies-arrayexpress
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:Bacteria commonly adapt to stresses by altering gene expression. To understand the response of M. tuberculosis (MTB) to various antibacterial agents, we performed transcriptomics on MTB bacilli exposed to several test compounds as well as known drugs (capreomycin, cycloserine, ethionamide, isoniazid, kanamycin, moxifloxacin, PA-824, rifampicin, streptomycin).
2015-11-11 | GSE71200 | GEO