Mycobacterium tuberculosis m4C DNA methyltransferase Rv3204 promotes mycobacteria survival under oxidative stress
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ABSTRACT:
PROVIDER: PRJNA586773 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10377454_1.fastq.gz | Fastqsanger.gz | |||
| SRR10377454_2.fastq.gz | Fastqsanger.gz | |||
| SRR10377455_1.fastq.gz | Fastqsanger.gz | |||
| SRR10377455_2.fastq.gz | Fastqsanger.gz | |||
| SRR10377456_1.fastq.gz | Fastqsanger.gz |
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Project description:ROS can damage cellular components and is a key player in many cellular signaling. Tuberculosis remains a major global public health concern largely due to the ability of its causative agent-Mycobacterium tuberculosis (Mtb) to subvert ROS toxicity. DNA methylation deficiency was previously shown to attenuate the Mtb virulence. But the role of DNA methyltransferase in Mycobacteria survival and the link with ROS are unknown. Mycobacterial protein Rv3204 is a DNA methyltransferase specific for N4-methylcytosine instead of N6-methyladenine (m6A) or 5-methylocytosine (m5C). The survival rate of m4C methyltransferase deletion mutants was lowered, accompanied by higher accumulation of ROS and failure of upregulating the transcription of gene engaged in ROS clearance upon rifampin(Rif) exposure.
2019-11-01 | GSE139646 | GEO
Project description:Purified NK cells were co-cultured with M. bovis BCG or M. tuberculosis H37Rv (1:1) in the presence of IL-2 (100U/ml) or IL-12 (10pg/ml) for 24h before trizol extraction. We used microarrays to detail the global gene expression underlying NK cell activation by mycobacteria. NK cell were isolated from the blood of 6 independent donors and activated with different mycobacteria and cytokines in order to study their transcriptional profiles according to mycobacterial virulence.
2011-07-26 | E-GEOD-30950 | biostudies-arrayexpress
Project description:Previous studies suggest that type I and type II CRISPR-Cas systems were employed to evade host immunity by targeting interference of bacteria’s own genes. Although Mycobacterium bovis (M. bovis) and Mycobacterium tuberculosis (M. tuberculosis) possess integrated type III-A CRISPR-Cas system, its role in mycobacteria remains obscure. Here, we observed that seven cas genes (csm2~6, cas10, cas6) were significantly upregulated under oxidative stress treatment. To explore the function of type III-A CRSIRP-Cas system, Total CRISPR system (TCR) mutant strain was generated in M. bovis Bacille Calmette-Guérin (BCG). Deletion of TCR results in increased sensitivity in response to H2O2 and reduced cell envelope integrity. By using RNA-Seq, 590 differential expression genes were found in mutant for TCR, of which 220 genes were upregulated and 370 genes were downregulated, indicating an important role of TCR in controlling gene expression in mycobacteria. Consistently, disrupting TCR results in poor intracellular survival in vivo and in vitro. Moreover, we showed for the first time that TCR contributed to the regulation of regulatory T cell population, supporting a role of TCR in modulating host immunity. These observations demonstrate that type III-A CRISPR-Cas system as an important factor for intracellular survival and host immunoregulation in mycobacteria, may be a potential target for therapy.
2021-02-05 | GSE166137 | GEO
Project description:Tuberculosis, caused by the pathogen Mycobacterium tuberculosis is a worldwide public health threat. Mycobacterium tuberculosis is capable of resisting of various stresses in host cells including high levels of ROS and copper ions. To better understand the resistance mechanisms of mycobacteria to copper, we generated a copper-resistant strain of Mycobacterium smegmatis, mc2155-Cu from the selection of copper sulfate treated-bacteria. The mc2155-Cu strain has the 5-fold higher resistance to copper sulfate and the 2-fold higher resistance to isoniazid (INH) than its parental strain mc2155, respectively. Quantitative proteomics was carried out to find differentially expressed proteins between mc2155 and mc2155-Cu. Among 345 differentially expressed proteins, copper-translocating P-type ATPase was up-regulated, while all other ABC transporters were down-regulated in mc2155-Cu, suggesting copper-translocating P-type ATPase plays a crucial role in copper resistance. Results also indicated that the down-regulation of metabolic enzymes and decreases in cellular NAD, FAD, mycothiol, and glutamine levels in mc2155-Cu were responsible to its slow growth rate as compared to mc2155. Down-regulation of KatG2 expression in both protein and mRNA levels indicates the co-evolution of copper and INH resistance in copper resistance bacteria, and provides new evidences to understanding of the molecular mechanisms of survival of mycobacteria under stress conditions.
2016-04-13 | PXD001989 | Pride
Project description:Purified NK cells were co-cultured with M. bovis BCG or M. tuberculosis H37Rv (1:1) in the presence of IL-2 (100U/ml) or IL-12 (10pg/ml) for 24h before trizol extraction. We used microarrays to detail the global gene expression underlying NK cell activation by mycobacteria.
2011-07-27 | GSE30950 | GEO
Project description:Tuberculosis claims nearly 2 million lives annually and its causative agent Mycobacterium tuberculosis is a highly successful pathogen which explores multiple signalling mechanisms to grow and survive in humans for decades. Well-studied protein kinase B (PknB), one of the 11 serine/threonine kinases present in M. tuberculosis, is critical for growth in vitro and in vivo. Here we demonstrate that PknB-depleted mycobacteria can normally replicate and synthesise peptidoglycan in osmoprotective medium. Comparative phosphoproteomics of PknB-producing and PknB-depleted mycobacteria identifies CwlM as a major PknB substrate. Complementation studies of cwlM mutant further support CwlM phosphorylation as the molecular basis for the PknB essentiality. We demonstrate that in growing mycobacteria CwlM is produced in two forms with distinct functions which are essential for growth: a non-phosphorylated membrane-associated CwlM and a PknB-phosphorylated cytoplasmic CwlM. Immunoprecipitation and mycobacterial two hybrid assays reveal partner proteins for phosphorylated and non-phosphorylated CwlM forms, as FhaA, a forkhead-associated domain protein, and MurJ (MviN), a predicted Lipid II flippase, respectively. We propose that PknB is not required for mycobacterial division but coordinates peptidoglycan polymerization and cross-linking by a novel CwlM-mediated mechanism
2018-09-24 | PXD009239 | Pride
Project description:Some intracellular bacteria are known to cause long-term infections for periods of time that last decades without compromising the viability of the host. Although of critical importance, the changes that intracellular bacteria suffer during this long process of residence in a host cell environment remain obscure. Here, we report an experimental approach to study the adaptations of intracellular mycobacteria forced by a long-term intracellular lifestyle. Long-term infection of host macrophages with mycobacteria was maintained for a period of years. Mycobacteria in the long-term infected macrophages underwent an adaptation process leading to impaired phenolic glycolipids (PGL) synthesis, preference for glucose as a carbon source and neutral lipids accumulation. These changes correlated with increased survival of mycobacteria in macrophages and mice during re-infection and specific expression of stress- and survival-related genes. Our findings identify bacterial traits implicated in the establishment of long-term cellular infections and represent a tool for understanding the physiological states of bacteria living in fluctuating intracellular environments.
2014-12-31 | GSE49976 | GEO
Project description:Mouse macrophages J774A.1 were pre-treated with the anti-inflammatory lipid eicosapenaenoic acid (EPA) or the pro-inflammatory lipid ceramide (Cer) for 3h. Macrophages were then infected with Mycobacterium smegmatis for 1h, and total RNA was collected. In a parallel experiment, infected macrophages were infected for 1h, 4h and 24h. At these time points, macrophages were lysed, bacteria was collected and quantified by the Colony Forming Units (CFU) Assay. This provided the kinetics of the killing of Mycobacteria inside mouse macrophages. CFU experiments revealed that cells pre-treated with EPA showed an increased number of bacteria inside macrophages, in contrast to cells pre-treated with Cer. To dissect the molecular mechanisms involved in the survival and killing of mycobacteria infected macrophages, mediated by lipids, gene expression studies were performed.
2015-01-20 | GSE27277 | GEO
Project description:Sputum expectorated by the pulmonary tuberculosis patients still remains a primary diagnostic specimen. The expression pattern of mycobacteria in sputum will lead to an insight of bacterial adaptation at the most highly transmissible stage of infection and can also help in identifying newer diagnostic as well as drug targets. Further, the identification of crossreactive gene targets from the sputum samples of other lung diseases will help to find the diagnostic candidates which will be highly specific to pulmonary tuberculosis.
2017-04-18 | GSE93316 | GEO
Project description:Rationale: Tuberculosis has a devastating impact on global health by claiming nearly 1.4 million lives each year. During infection Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, produces heterogenous populations some of which don’t produce colonies on agar but grow in liquid media and often require supplementation with culture supernatants or recombinant Resuscitation-promoting factor, thus defined as differentially culturable bacilli. Objectives: to evaluate whether exposure to nitric oxide (NO), a well-known host defence molecule, alters mycobacterial growth phenotypes and drives generation of Rpf-dependent differentially culturable bacilli. Methods: a novel NO donor was synthesised and tested against Mtb and Mycobacterium bovis BCG in vitro, followed by growth assays, flow cytometry analysis and assessment of transcriptomic responses. Resuscitation-promoting factor (Rpf) inhibitors were used to characterise the role of Rpf proteins in the reactivation of NO-treated mycobacteria. Mycobacterial phenotypes were also investigated during infection of THP-1 macrophages activated with retinoic acid and vitamin D3. Measurements and Main Results: differentially culturable mycobacteria were generated after exposure to the novel NO donor or during infection of activated THP-1 cells. Resuscitation of these differentially culturable bacilli was largely abolished by specific Rpf inhibitors. Transcriptomic analysis revealed redox-associated stress signatures mediated by SigH and SigF, with significant down-regulation of ribosome and cell wall architecture genes, including rpfA, rpfB and rpfE, and induction of genes involved in response to thiol stress, sulphur metabolism and iron acquisition. Conclusion: Our study provides mechanistic insights into the generation of Rpf-dependent Mtb during tuberculosis and outlines a critical role of NO in this process.
2023-09-01 | E-MTAB-10776 | biostudies-arrayexpress