Genome-wide gene expression profiling of anti-tuberculosis drugs-treated macrophages
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ABSTRACT:
PROVIDER: PRJNA601453 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10899321.fastq.gz | Fastqsanger.gz | |||
| SRR10899322.fastq.gz | Fastqsanger.gz | |||
| SRR10899323.fastq.gz | Fastqsanger.gz | |||
| SRR10899324.fastq.gz | Fastqsanger.gz | |||
| SRR10899325.fastq.gz | Fastqsanger.gz |
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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:Transcriptional Response of Mycobacterium tuberculosis H37Rv to Anti-TB drugs
| PRJNA489663 | ENA
Project description:The direct communication between our central nervous and inflammatory signalling systems is a well-recognised, yet poorly understood relationship. To increase our understanding of this relationship, we examined the metabolism of serotonin and its precursor tryptophan in macrophages under inflammatory settings. Both are involved in inflammatory signalling and known to play a major role in mood regulation. Tryptophan depletion by macrophages during inflammation can consequently result in a reduction of serotonin systemically and has been suggested to cause depression. Increased understanding of this system could help overcome the problem of treatment resistant depressed patients. To this end, we treated primary human monocyte derived macrophages with a range of anti-depressant/anti-inflammatory drugs and analysed their transcriptional profile under various inflammatory conditions. In addition to the classic endotoxic driver of inflammation, LPS, we also used IFNα which is a constitutive cytokine shown to directly induce depression when administered in high doses. The anti-depressant drugs were not found to have any significant effects on macrophage inflammatory signalling. However, the anti-inflammatories drugs were found to alter components of the serotonin/tryptophan metabolism pathways. This study increases our understanding of the intricacies of immune/mood cross-talk and offers into developing anti-inflammatories as co-treatment for depression. We treated human primary macrophage cells with anti-inflammatory or anti-depressant drugs and analysed their transcriptional effects during inf.lammatory signaling within the context of tryptophan metabolism/kynurenic metabolism.
2018-01-01 | GSE85333 | GEO
Project description:We report the application of next generation sequencing technology for high-throughput profiling of total RNA to determine the expression of all genes expressed in human primary hepatocytes derived from three healthy (drug/tobacco/alcohol free) volunteers in response to anti-tuberculosis antibiotics, including, rifampin, rifabutin and rifapentine through comparison with gene profiles of vehicle (methanol) treated and untreated cells. We determined the response of over 22,000 genes expressed in human primary hepatocytes following rifampin, rifabutin and rifapentine treatment for 72h. We found that several drug metabolizing enzymes, including cytochrome P450 3A4 and drug transporters are differentially expressed in human primary hepatocytes in response to rifamycin antibiotics. We utilized the information generated with differential gene expression study to determine interaction of rifamyicn antibiotics with antiviral, antibacterial, antifungal agents and other drugs used to treat several ailments in tuberculosis patients. This study provides a comprehensive profiles of genes expressed in response to rifamycin antibiotics towards characterization of their drug interactions with the drugs that are combined to treat various viral, bacterial, fungal and other diseases, including cancer.
2020-03-26 | GSE139896 | GEO
Project description:The pathogenesis of liver damage induced by anti-tuberculosis drugs is not fully understood, andcurrently, there is no clinically useful biomarker for early diagnosis and treatment.By comparing the differences in the expression of global gene transcripts in the serum of patients with and without anti-tuberculosis drugs induced liver injury, dysregulation genes not only provides a basis for studying pathogenesis, but also provides important information to find new targets for diagnosis and treatment of disease. We used microarrays to detail the global programme of gene expression in sera underlying anti-tuberculosis drug-induced liver injury and identified distinct classes of transcript during this process.
2021-01-01 | GSE141362 | GEO
Project description:The antimicrobials isoniazid and pyrazinamide, used for the treatment of tuberculosis are known to cause drug-induced liver injury in humans. This limits the effectiveness of tuberculosis treatment, resulting in incomplete cure, relapse and the development of antimicrobial resistance. MicroRNAs are known to be good biomarkers of disease, with the microRNA miR-122 being diagnostic for liver injury. In this study zebrafish larvae were exposed to the anti-tuberculosis drugs isoniazid and pyrazinamide at concentrations which demonstrated liver injury by microscopy and histology. The aim of this study is to understand small RNA changes occurring in anti-tuberculosis drug-induced liver injury and to attempt to identify novel microRNA biomarkers of liver injury.
2023-12-25 | GSE146260 | GEO
Project description:Various anti-mycoplasma drugs have different effects on cells growth We used microarrays to detail the global programme of gene expression underlying gastric cancer cells treated with anti-mycoplasma drugs and identified distinct classes of up-regulated genes during this process.
2015-10-08 | GSE73777 | GEO
Project description:Background: Anti-tuberculosis drugs, mainly developed more than 60 years ago, combined with a poorly effective vaccine, have failed to eradicate tuberculosis. More worryingly, multi-resistant strains of Mycobacterium tuberculosis are constantly emerging. Innovative strategies are thus urgently needed to improve tuberculosis treatment. Recently, host-directed therapy (HDT) has emerged as a promising strategy to be used in adjunct with existing or future antibiotics, by improving innate immunity or limiting immunopathology. Here, we evaluated the impact of two host-directed compounds, namely MC3465 and MC3209, on the response of human monocytes-derived macrophages infected with Mycobacterium tuberculosis (MTB). Results: The expression of 181 genes was differentially regulated following MC3465 treatment (p-value < 0.05, log FC ≥ 0.5 and ≤ -0.5) after 4 h, with 53 being upregulated and 128 being downregulated. The expression of more genes was affected after 24h of treatment. 224 genes were upregulated and 652 genes downregulated. (p value < 0.05, log FC ≥ 0.5 and ≤ -0.5). We classified those differentially expressed genes by performing gene-set enrichment analysis using ClueGO cluster analysis. The gene set downregulated by MC3465 at 4 h was significantly enriched for genes associated with chemotaxis and cellular zinc ion homeostasis and cell chemotaxis. At 24 h, most of the downregulated genes belongs to the innate immune response and the cytokine response, with many genes belonging to the type I IFN pathway. Conclusions: Our results indicate that MC3465 alters zinc homeostasis in human macrophages.
2024-03-04 | GSE222412 | GEO
Project description:Gene signatures of rifampin, rifabutin an rifapentine anti-tuberculosis drugs in human primary hepatocytes.
| PRJNA587490 | ENA
Project description:RNA-seq analysis to assess the effect of different drugs (34503, 36009, 34503, 36018, Moxi) on Mycobacterium tuberculosis compared to untreated control cells (DMSO).
2022-12-31 | E-MTAB-12306 | biostudies-arrayexpress