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Intricate genetic program underlying hypoxia-induced dormancy in Mycobacterium tuberculosis revealed by high-resolution transcriptional time-course

ABSTRACT: Intricate genetic program underlying hypoxia-induced dormancy in Mycobacterium tuberculosis revealed by high-resolution transcriptional time-course

PROVIDER: PRJNA478238 | ENA |

REPOSITORIES: ENA

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Intricate genetic program underlying hypoxia-induced dormancy in Mycobacterium tuberculosis revealed by high-resolution transcriptional time-course

Project description:Transcriptional profiling (RNA-seq) of Mycobacterium tuberculosis during transitions between normoxia and hypoxia.

2019-03-04 | GSE116353 | GEO

Effect of INH treatment on Mycobacterium tuberculosis gene expression in various dormancy models.

Project description:These data represent the expression patterns of Mycobacterium tuberculosis in progressive hypoxia, nutrient depletion, and in-vivo hollow fiber models of dormancy. The assumptions are that the set of genes that respond to INH treatment during Log phase growth would not be differentially regulated during INH treatment in the dormancy models, and that the overall number of differentially regulated genes would be reduced do to the low metabolic state of the cells. Keywords: Dormancy Model Drug Response Comparison

2007-12-14 | GSE9776 | GEO

Lysine acetylation of DosR regulates the hypoxia response of Mycobacterium tuberculosis

Project description:Tuberculosis caused by Mycobacterium tuberculosis (Mtb) infection remains a huge global public health problem. One striking characteristic of Mtb is its ability to adapt to hypoxia, and thus ensuing transition to dormant state for persistent infection, but how the hypoxia responses of Mtb is regulated remains largely unknown. Here, we performed a quantitative acetylome analysis to compare the acetylation profile of Mtb under aeration and hypoxia, and showed that 377 acetylation sites in 269 proteins of Mtb were significantly change under hypoxia. Especially, deacetylation of Dormancy Survival Regulator (DosR) at K182 promoted the hypoxia response of Mtb and enhanced transcription of DosR-targeted genes. Mechanistically, recombinant DosRK182R protein demonstrated enhanced DNA-binding activity in comparison with DosRK182Q protein. Moreover, Rv0998 was identified as an acetyltransferase that mediates the acetylation of DosR at K182. Deletion of Rv0998 also promoted the adaption of Mtb to hypoxia and transcription of DosR-targeted genes. Mice infected with Mtb strain containing acetylation-defective DosRK182R or lacking Rv0998 had much lower bacterial counts, and less severe histopathological impairments compared with those infected with the wild-type strain. Our findings suggest that hypoxia induces the deacetylation of DosR, which in turn increases its DNA binding ability to promote the transcription of target genes, allowing Mtbto transit to dormancy under hypoxia.

2018-10-22 | PXD008587 | Pride

Comparative label-free lipidomic analysis of Mycobacterium tuberculosis during dormancy and reactivation

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

BCG vaccine strains lack narK2 and narX induction and exhibit altered phenotypes during dormancy

Project description:Mycobacterium tuberculosis is the causative agent of tuberculosis, a disease that affects one-third of the world’s population. The sole extant vaccine for tuberculosis is the live attenuated Mycobacterium bovis bacille Calmette-Guerin (BCG). We examined 13 representative BCG strains from around the world to ascertain their ability to express DosR-regulated dormancy antigens. These are known to be recognized by T-cells of M. tuberculosis infected individuals, especially those harboring latent infections. Differences in expression of these antigens could be valuable for use as diagnostic markers to distinguish BCG vaccination from latent tuberculosis. We determined that all BCG strains were defective for induction of two dormancy genes, narK2 (Rv1737c) and narX (Rv1736c). NarK2 is known to be necessary for nitrate respiration during anaerobic dormancy. Analysis of the narK2/X promoter region revealed a base substitution mutation in all tested BCG strains and M. bovis in comparison to the M. tuberculosis sequence. We also show that nitrate reduction by BCG strains during dormancy was greatly reduced compared to M. tuberculosis and varied between tested strains. Several dormancy regulon transcriptional differences were also identified among the strains, as well as variation in their growth and survival. These findings demonstrate defects in DosR regulon expression during dormancy and phenotypic variation between commonly used BCG vaccine strains. 12 different BCG strains were examined as well as M. tuberculosis H37Rv and M. bovis. Two arrays per strain were analyzed, one with the addition of nitric oxide and the other utilizing hypoxia treatment, both conditions shown to induce expression of the dormancy regulon. The reference sample for each array was log phase M. tuberculosis H37Rv.

2008-05-03 | E-GEOD-11315 | biostudies-arrayexpress

Quantitative Proteomics Reveals Dormancy Related Proteins Mediated Attenuation Program in Mycobacterium Strain

Project description:To better understand the virulence difference among different MTB strains and identify new targets for therapeutic intervention under hypoxia condition, we compared the global protein expression at the protein level by quantitative proteomics among H37Rv, H37Ra and BCG.

2022-04-04 | PXD023788 | Pride

Quantitative Proteomics Reveals Dormancy Related Proteins Mediated Attenuation Program in Mycobacterium Strain

2022-04-01 | PXD017174 | Pride

Seasonal bud dormancy progression

Project description:This study investigated changes in the transcriptome of outdoor grown leafy spurge crown buds as they progress from paradormancy in August and September into endo dormancy in October through to ecodormancy in November and December. Keywords: Dormancy leafy spurge adventitious-buds

2007-08-24 | GSE8849 | GEO

Bud dormancy in different peach cultivars

Project description:Correlation analysis of the expression of bud dormancy-related genes in 10 peach cultivars, with different chilling requirements for dormancy release.

2012-01-15 | E-MEXP-3201 | biostudies-arrayexpress

affy_sunflower_2010_13-ROS and hormones in sunflower seed dormancy.

Project description:affy_sunflower_2010_13 - affy_sunflower_2010_13 - It concerns the interaction between ROS and hormones in dormancy release in sunflower seeds. ABA is responsible for dormancy maintenance, while GA and ethylene promote seed germination. Based on our results, ROS could represent good candidate to shift from a hormone signalling to another determining the dormancy state in sunflower seeds.-We aim to understand the mechanisms controlling sunflower seed dormancy at the transcriptomic level, by the application of treatments which maintain dormancy as ABA, or alleviate dormancy as ROS and ethylene. Transcripts comparison will be performed between dormant and non-dormant sunflower embryo imbibed 24h on water, on ABA, on methylviologen, a pro-oxidant compound or on ethylene. 12 arrays - SUNFLOWER; treated vs untreated comparison

2013-08-01 | E-GEOD-44165 | biostudies-arrayexpress

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