Transcriptional changes during Mycobacterium tuberculosis reactivation from persistence
Ontology highlight
ABSTRACT:
ORGANISM(S): Mycobacterium tuberculosis H37Rv
PROVIDER: GSE83814 | GEO | 2016/12/31
SECONDARY ACCESSION(S): PRJNA327080
REPOSITORIES: GEO
Similar Datasets
Project description:Lysates of Mycobacterium tuberculosis (H37Rv auxotroph mc(2)6020) grown under various conditions (normoxia, hypoxia, reactivation from hypoxia) probed the serine hydrolase probe with ActivX-desthiobiotin FP.
2016-10-10 | MSV000080238 | MassIVE
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: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:These data represent the global gene expression profile of Mycobacterium tuberculosis after 24 hrs and 72 hrs of inorganic phosphate starvation. Differentially regulated genes appear to include those encoding proteins involved in adaptation to phosphate starvation, namely those involved in phosphate regulation and phosphate assimilation, as well as those involved in the stringent response.
2009-09-22 | GSE14840 | GEO
Project description:The isogenic Mtb:ΔRv2745c mutant is significantly more sensitive normoxia conditions after a period of hypoxia, relative to wild-type Mtb, implicating a role for ClgR in response to reactivation, in vivo. Both hypoxia and reaeration treatment led to dysregulation of the σH regulon in the isogenic mutant, Mtb:ΔRv2745c. Induction of clgR in Mtb did lead to Clp protease induction, indicating that clgR plays a role in differntially activating downstream genes in a condition dependent manner. Disruption of genes involved in the dosR regulon, the Enduring Hypoxia Response, lipid synthesis, and mycolic acid synthesis also occurred in the knock out, implicating clgR as a possible regulator of downstream signaling cascades that facilitate Mtb survival. There was also a differnetial response of genes that are known Clp protease targets, in addition to potential Clp protease targets that had similar induction patterns as known Clp protease targets. At different time points, following hypoxia (day 1, day 5, and day 7) and reaeration (1 hour, 4 hour, 6 hour, 12 hour, 24 hour, and 48 hour) treatments M. tuberculosis CDC1551 cultures, RNA was extracted and labeled with Cy5. RNA was also extracted from pre-hypoxia (t=0) time points and labeled with Cy3. These samples were cohybridized on M. tuberculosis CDC1551 whole genome microarrays using biological triplicate samples (i.e. samples derived from three distinct cultures and treatments) and thus three unique datasets were generated for each of the three time points for Mtb. Similar experiments were performed for an isogenic Rv2745c (clgR) mutant in Mtb CDC1551 which was generated by allelic exchange.
2014-12-12 | E-GEOD-64065 | biostudies-arrayexpress
Project description:Mycobacterium tuberculosis can persist for years in the hostile environment of the host in a non-replicating or slowly replicating state. While active disease predominantly results from reactivation of a latent infection, the molecular mechanisms of M. tuberculosis reactivation are still poorly understood. We characterized the physiology and global transcriptomic profiles of M. tuberculosis during reactivation from hypoxia-induced non-replicating persistence. We found that M. tuberculosis reactivation upon reaeration was associated with a lag phase, in which the recovery of cellular physiological and metabolic functions preceded the resumption of cell replication. Enrichment analysis of the transcriptomic dynamics revealed changes to many metabolic pathways and transcription regulons/subnetworks that orchestrated the metabolic and physiological transformation in preparation for cell division. In particular, we found that M. tuberculosis reaeration lag phase is associated with down-regulation of persistence-associated regulons/subnetworks, including DosR, MprA, SigH, SigE, and ClgR, as well as metabolic pathways including those involved in the uptake of lipids and their catabolism. More importantly, we identified a number of up-regulated transcription regulons and metabolic pathways, including those involved in metal transport and remobilization, second messenger-mediated responses, DNA repair and recombination, and synthesis of major cell wall components. We also found that inactivation of the major alternative sigma factors SigE or SigH disrupted exit from persistence, underscoring the importance of the global transcriptional reprogramming during M. tuberculosis reactivation. Our observations suggest that M. tuberculosis lag phase is associated with a global gene expression reprogramming that defines the initiation of a reactivation process.
| S-EPMC5005354 | biostudies-literature
Project description:Tuberculosis (TB) remains one of the world’s major infectious diseases affecting nations with limited public health resources. Multidrug resistance development has seriously compromised therapeutic treatment choices. The pathology of latent TB shows evidence of a reservoir of Mycobacterium tuberculosis (Mtb) in the lungs of affected individuals. If the pathogen is contained by the immune system, no overt disease symptoms occur. The environmental and internal triggers leading to disease reactivation are not well understood. Proteomic investigations of blood plasma and sputum derived from subjects with active TB versus latent TB versus healthy individuals may yield new biomarkers and, when surveying larger longitudinally monitored cohorts, may discriminate infection outcomes in an endemic setting.
2021-05-26 | PXD012412 | Pride
Project description:Transcriptional changes during Mycobacterium tuberculosis reactivation from persistence
| PRJNA327080 | ENA
Project description:A potent Th1 immune response is critical to the control of tuberculosis. The impact of an additive Th2 response on the course of disease has so far been insufficiently characterized, despite increased morbidity after coinfection with Mycobacterium tuberculosis and Th2 eliciting helminths and possible involvement of Th2 polarization in reactivation of latent tuberculosis. Here, we describe the gene expression profile of murine bone marrow derived macrophages alternatively activated by IL-4 to infection with M. tuberculosis. Comparison of transcriptional profiles of infected IL-4 and IFN-g activated macrophages revealed delayed and partially diminished responses in alternatively activated macrophages, characterized by reduced exposure to nitrosative stress and increased iron availability, respectively, to intracellular bacteria. Alternative activation of host macrophages correlated with elevated expression of the M. tuberculosis iron storage protein bfrB as well as reduced expression of the mycobactin synthesis genes mbtI and mbtJ. The extracellular matrix remodelling enzyme matrix metalloproteinase-12 (MMP-12) was induced in alternatively activated macrophages in vitro, and MMP-12 expressing macrophages were abundant at late, but not early, stages of tuberculosis in murine lungs. Our findings emphasize that alternative activation deprives macrophages of control mechanisms which limit mycobacterial growth in vivo, thus supporting intracellular persistence of M. tuberculosis. Keywords: transcriptome, gene regulation, macrophages, IL-4, IFN-gamma, nitric oxide
2006-01-01 | GSE3552 | GEO
Project description:We analyzed the genes expressed, or the transcriptome, of bacilli (Mycobacterium tuberculosis) growing in fatty acids as sole carbon source. Using new technologies to massively sequence of RNA molecules we identified a group of genes that provides novel insight regarding the metabolic pathways and transcriptional regulation of latent M. Tuberculosis.
2013-06-13 | GSE47863 | GEO