Dormant Mycobacterium tuberculosis cluster
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB48947 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR7421585_1.fastq.gz | Fastqsanger.gz | |||
| ERR7421585_2.fastq.gz | Fastqsanger.gz | |||
| ERR7421586_1.fastq.gz | Fastqsanger.gz | |||
| ERR7421586_2.fastq.gz | Fastqsanger.gz | |||
| ERR7421866_1.fastq.gz | Fastqsanger.gz |
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Project description:Insights on the complexity of a dormant Mycobacterium tuberculosis cluster after its transmission is resumed
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Project description:Dormant cells of Mycobacterium tuberculosis, in addition to low metabolic activity and a high level of drug resistance, are characterized by ‘non-culturability’ – a specific reversible state of the inability of the cells to grow on solid media. The biochemical characterization of this physiological state of the pathogen is only superficial, pending clarification of the metabolic processes that may exist in such cells. In this study, applying LC-MS proteomic profiling, we report the analysis of proteins accumulated in dormant, ‘non-culturable’ M. tuberculosis cells in an in vitro model of self-acidification of mycobacteria in the post-stationary phase, simulating the in vivo persistence conditions. This approach revealed the preservation of 1379 proteins in cells after 5 months of storage in dormancy; among them, 468 proteins were statistically different from those in the actively growing cells and bore a positive fold change (FC). Differential analysis revealed the proteins of the pH-dependent regulatory system PhoP and allowed the reconstruction of the reactions of central carbon/glycerol metabolism, as well as revealing the salvaged pathways of mycothiol and UMP biosynthesis, establishing the cohort of survival enzymes of dormancy. The annotated pathways mirror the adaptation of the mycobacterial metabolic machinery to life within lipid-rich macrophages: especially the involvement of the methyl citrate and glyoxylate pathways. Thus, the current in vitro model of M. tuberculosis self-acidification reflects the biochemical adaptation of these bacteria to persistence in vivo. Comparative analysis with published proteins displaying antigenic properties makes it possible to distinguish immunoreactive proteins among the proteins bearing a positive FC in dormancy, which may include specific antigens of latent tuberculosis. Additionally, the biotransformatory enzymes (oxidoreductases and hydrolases) capable of prodrug activation and stored up in the dormant state were annotated. These findings may potentially lead to the discovery of immunodiagnostic tests for early latent tuberculosis and trigger the discovery of efficient drugs/prodrugs with potency against non-replicating, dormant populations of mycobacteria.
2022-07-07 | PXD028849 | Pride
Project description:Mycobacterium tuberculosis employs several strategies to combat and adapt to adverse conditions encountered inside the host. The non-replicative dormant state of the bacterium is linked to drug resistance and slower response to anti-tubercular therapy. It is known that alterations in lipid content allow dormant bacteria to acclimatize to cellular stress. Employing comparative lipidomic analysis we profiled the changes in lipid metabolism in M. tuberculosis using a modified Wayne's model of hypoxia-induced dormancy. Further we subjected the dormant bacteria to resuscitation, and analyzed their lipidomes until the lipid profile was similar to that of normoxially grown bacteria. An enhanced degradation of cell wall-associated and cytoplasmic lipids during dormancy, and their gradual restoration during reactivation, were clearly evident. This study throws light on distinct lipid metabolic patterns that M. tuberculosis undergoes to maintain its cellular energetics during dormancy and reactivation.
2018-10-22 | MTBLS304 | MetaboLights
Project description:Transcriptional response of THP-1 cells infected with Mycobacterium tuberculosis utilizing ‘Active’ Mtb and ‘Dormant’ Mtb infection models at different time points. Analysis of the transcriptomic data deciphered the perturbation of gamut of host cellular pathways that are common and differentially manifested in the ‘Active’ Mtb and ‘Dormant’ Mtb infection models.
2023-02-01 | GSE207580 | GEO
Project description:resequencing of Mycobacterium tuberculosis isolates from a Beijing cluster
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Project description:Nowadays proteomics is the one of the major instruments for editing and correct decryption of genomic information. Genomic correction of socially significant pathogens, like Mycobacterium tuberculosis, is by far the most relevant. We conducted proteogenomic analysis of W-148 strain, which belong to the Beijing B0/W148 cluster. Strains of this cluster possess unique pathogenic properties and have a unique genome organization. Taking into account a high similarity of cluster strains at the genomic level we analysed MS/MS datasets obtained for 63 clinical isolates of Beijing B0/W148. Based on H37Rv and W-148 annotations we identified 2,546 proteins, representing more than 60 % of total proteome. A set of peptides (n=404), specific for W-148 was found in comparison with H37Rv. Start sites for 32 genes were corrected based on combination of LC-MS/MS proteomic data with genomic six frame translation. Additionally, presence of peptides for 10 pseudogenes has been confirmed. Thus, the data obtained by us undoubtedly shows the need for conducting genome annotation based on proteomic data. Corrected during the study W-148 genome annotation will allow to use it in studies on Beijing B0/W148 cluster strains.
2018-10-08 | PXD009489 | Pride
Project description:Mycobacterium tuberculosis Beijing B0/W148 is one of the most widely distributed clusters in the Russian Federation and in some countries of the former Soviet Union. Recent studies have improved our understanding of the reasons for the “success” of the cluster but this area remains incompletely studied. Here, we focused on the system omics analysis of the RUS_B0 strain belonging to the Beijing B0/W148 cluster. Completed genome sequence of RUS_B0 (CP020093.1) and a collection of WGS for 200 cluster strains from the NCBI were used to describe the main genetic features of the population, as well as the level of resistance. In turn, proteome and transcriptome studies allowed to confirm the genomic data and to identify a number of finds that have not previously been described. Our results demonstrate that expression of the whiB6 which contains cluster-specific polymorphism (T4338371G) increased by more than 50 times in RUS_B0. Additionally, the level of ethA transcripts in RUS_B0 is increased almost 30 times compared to the H37Rv. Start sites for 10 genes were corrected based on the combination of proteomic and transcriptomic data. Additionally, based on the omics approach, we identified 5 new genes.
2020-05-26 | PXD013509 | Pride
Project description:Tuberculosis, caused by Mycobacterium tuberculosis, still remains a major global health problem. The main obstacle in eradicating this disease is the ability of this pathogen to remain dormant in macrophages, and to get reactivated later under immuno-compromised conditions. The physiology of hypoxic nonreplicating M. tuberculosis is well studied using many in vitro dormancy models. However, the physiological changes that take place during the shift from dormancy to aerobic growth (reactivation) have rarely been subjected to a detailed investigation. In this study, we developed an in vitro reactivation system by re-aerating bacteria that were made dormant employing Wayne’s dormancy model, and compared the proteome profiles of dormant and reactivated bacteria using label-free one-dimensional LC/MS/MS analysis.
2015-06-01 | PXD001158 | Pride
Project description:Host-pathogen interactions in Mycobacterium tuberculosis infection still remain poorly understood. We investigated the host immune response to different reference Mycobacterium tuberculosis strains in THP-1 cells. Major differences in the gene expression profiles were identified in response to infection with these strains. These findings shed new insights into the dynamic variation in tuberculosis immune response and pathogenesis. We used Affymetrix GeneChip Human Exon 1.0 ST microarrays to investigate host differential gene expression in response to different Mycobacterium tuberculosis strains.
2024-10-24 | GSE246736 | GEO
Project description:Dormant Mycobacterium tuberculosis bacilli play important role in latent tuberculosis infection. Previously we have demonstrated that cultivation of M. tuberculosis in potassium-deficient media resulted in the generation of dormant ‘non-culturable’ cells. Addition of a moderate concentration of rifampicin enabled to kill a minor subpopulation of actively replicating bacilli and obtain a homogeneous ‘zero-CFU’ population of dormant cells characterized by total inability to produce colonies on solid media and by high potential to reactivate after reintroducing of potassium. An RNA-seq based transcriptome analysis of this dormant ‘zero-CFU’ population revealed a 30-50 fold decrease of the total level of mRNA in the cells, indicating global shift-down of gene expression level. The residual scarce protein-coding transcriptome of the dormant cells showed decreased abundance of mRNAs encoding ribosomal proteins and enzymes of TCA cycle and respiratory chain, and increased abundance of mRNAs encoding PE-PGRS proteins. Interestingly, the transcriptome of dormant cells showed little changes during several days of persistence. This stability of ‘dormant’ transcripts may reflect their readiness for translation upon resuscitation process. Transition of M. tuberculosis cells to dormancy was accompanied by the cleavage of 23S ribosomal RNA at a specific point, located outside the ribosome catalytic center. Another feature of the ‘dormant’ transcriptome was an increased abundance of non-coding transcripts. Enrichment of "dormant transcriptome" by small non-coding RNAs playing regulatory function in the cell probably indicates their role in transition to and maintenance of dormant ‘non-culturable’ state.
2015-06-01 | GSE66408 | GEO