Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1140188 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Tuberculosis is an infectious disease, with latent infection with Mycobacterium tuberculosis (M.tb) affecting 1/3 of humanity. It can remain quiescent for long time, making eradication very difficult. To do so, M.tb need to carefully orchestrate its gene expression to survive immune response and starvation but still be able to reactivate to enable transmission to new hosts. Here we used whole transcriptome deep sequencing to compare gene expression between wild type M.tb and a strain with its whiB6, a gene encoding a putative redox-sensing transcription factor, disrupted by a transposon. We found several genes associated with dormancy such as hspX, fdxA and narK2 upregulated in the transposon mutant, indicating that WhiB6 may be a repressor of such genes. The results suggest that WhiB6 may be a complement to the dosS/dosR system in regulating genes important for dormancy. Triplicate cultures of a mutant with its whiB6 gene disrupted by a transposon and wild-type M. tuberculosis CDC1551 were grown in 7H9 media. RNA was extracted and depleted from rRNA. Global gene expression was measured using AB SOLID RNA sequencing.
2013-09-18 | E-GEOD-40941 | biostudies-arrayexpress
Project description:Tuberculosis is an infectious disease, with latent infection with Mycobacterium tuberculosis (M.tb) affecting 1/3 of humanity. It can remain quiescent for long time, making eradication very difficult. To do so, M.tb need to carefully orchestrate its gene expression to survive immune response and starvation but still be able to reactivate to enable transmission to new hosts. Here we used whole transcriptome deep sequencing to compare gene expression between wild type M.tb and a strain with its whiB6, a gene encoding a putative redox-sensing transcription factor, disrupted by a transposon. We found several genes associated with dormancy such as hspX, fdxA and narK2 upregulated in the transposon mutant, indicating that WhiB6 may be a repressor of such genes. The results suggest that WhiB6 may be a complement to the dosS/dosR system in regulating genes important for dormancy.
2013-09-18 | GSE40941 | GEO
Project description:Transcriptional profiling of SirR and manganese regulated expression of genes in Mycobacterium tuberculosis strains comparing high manganese vs. low manganese in Rv (wild type Mycobacterium tuberculosis) and ST70 (mntR mutant strain of Mycobacterium tuberculosis)
2015-12-08 | GSE70812 | GEO
Project description:The Mycobacterium tuberculosis genome encodes two complete high-affinity Pst phosphate-specific transporters. We previously demonstrated that a membrane-spanning component of one Pst system, PstA1, was essential both for M. tuberculosis virulence and for regulation of gene expression in response to external phosphate availability. To determine if the alternative Pst system is similarly required for virulence or gene regulation, we constructed a deletion of pstA2. Transcriptome analysis revealed that PstA2 is not required for regulation of gene expression in phosphate-replete growth conditions. PstA2 was also dispensable for replication and virulence of M. tuberculosis in a mouse aerosol infection model. However, a âpstA1âpstA2 double mutant was attenuated in mice lacking the cytokine interferon-gamma, suggesting that M. tuberculosis requires high-affinity phosphate transport to survive phosphate limitation encountered in the host. Surprisingly, âpstA2 bacteria were more resistant to acid stress in vitro. This phenotype is intrinsic to the alternative Pst transporter since a âpstS1 mutant exhibited similar acid resistance. Our data indicate that the two M. tuberculosis Pst transporters have distinct physiological functions, with the PstA1 transporter being specifically involved in phosphate sensing and gene regulation while the PstA2 transporter influences survival in acidic conditions. Aerobically growing logarithmic phase Wt or pstA2 mutant or pstA1A2 double mutant strains were grown in phosphate replete media and analyzed after several hours. Experiments were repeated in triplicate.
2016-06-29 | E-GEOD-83812 | biostudies-arrayexpress
Project description:To survive a dynamic host environment, Mycobacterium tuberculosis must endure a series of challenges from reactive oxygen and nitrogen stress, to drastic shifts in oxygen availability. The mycobacterial Lsr2 protein has been implicated in reactive oxygen defense via direct protection of DNA. To examine the role of Lsr2 in pathogenesis and physiology of M. tuberculosis, we generated a strain deleted for lsr2. Analysis of the M. tuberculosis ?lsr2 strain demonstrated that Lsr2 is not required for DNA protection, as this strain was as equally susceptible as the wild-type to DNA-damaging agents. The lsr2 mutant did display severe growth defects under normoxic and hyperoxic conditions, but was not required for growth under low oxygen conditions. However, it was also required for adaptation to anaerobiosis. The defect in anaerobic adaptation led to a marked decrease in viability during, as well as a lag in recovery from, anaerobiosis. Gene expression profiling of ?lsr2 under aerobic and anaerobic conditions in conjunction with published DNA binding-site data indicate that Lsr2 is a global transcriptional regulator controlling adaptation to changing oxygen levels. The ?lsr2 strain was capable of establishing an early infection in the Balb/c mouse model; however, it was severely defective in persisting in the lungs and caused no discernible lung pathology. These findings demonstrate M. tuberculosis Lsr2 is a global transcriptional regulator required for control of genes involved in adaptation to extremes in oxygen availability and is required for persistent infection. Wild type H37Rv or lsr2 mutant strains were grown aerobically or in a Rach dormancy model in dubos tween albumin media and analyzed. Alternately, either aerobically grown or Rach model hypoxic samples were challenged with H2O2 samples and harvested 1h later. Experiments were repeated in triplicate or quadruplicate.
2014-05-24 | E-GEOD-57948 | biostudies-arrayexpress
Project description:Transcriptional profiling of SirR and manganese regulated expression of genes in Mycobacterium tuberculosis strains comparing high manganese vs. low manganese in Rv (wild type Mycobacterium tuberculosis) and ST70 (mntR mutant strain of Mycobacterium tuberculosis) Two strains each with two conditions experiment, Rv (Mycobacterium tuberculosis wild type strain) high manganese vs. low manganese and ST70 (mntR mutant strain of Mycobacterium tuberculosis) high manganese vs. low manganese. Number of biological replicates is 3 for each condition for each strain.
2015-12-08 | E-GEOD-70812 | biostudies-arrayexpress
Project description:The Mycobacterium tuberculosis genome encodes two complete high-affinity Pst phosphate-specific transporters. We previously demonstrated that a membrane-spanning component of one Pst system, PstA1, was essential both for M. tuberculosis virulence and for regulation of gene expression in response to external phosphate availability. To determine if the alternative Pst system is similarly required for virulence or gene regulation, we constructed a deletion of pstA2. Transcriptome analysis revealed that PstA2 is not required for regulation of gene expression in phosphate-replete growth conditions. PstA2 was also dispensable for replication and virulence of M. tuberculosis in a mouse aerosol infection model. However, a ∆pstA1∆pstA2 double mutant was attenuated in mice lacking the cytokine interferon-gamma, suggesting that M. tuberculosis requires high-affinity phosphate transport to survive phosphate limitation encountered in the host. Surprisingly, ∆pstA2 bacteria were more resistant to acid stress in vitro. This phenotype is intrinsic to the alternative Pst transporter since a ∆pstS1 mutant exhibited similar acid resistance. Our data indicate that the two M. tuberculosis Pst transporters have distinct physiological functions, with the PstA1 transporter being specifically involved in phosphate sensing and gene regulation while the PstA2 transporter influences survival in acidic conditions.
2016-06-29 | GSE83812 | GEO
Project description:Fang2010 - Genome-scale metabolic network of
Mycobacterium tuberculosis (iNJ661m)
This model is described in the article:
Development and analysis of
an in vivo-compatible metabolic network of Mycobacterium
tuberculosis.
Fang X, Wallqvist A, Reifman
J.
BMC Syst Biol 2010; 4: 160
Abstract:
BACKGROUND: During infection, Mycobacterium tuberculosis
confronts a generally hostile and nutrient-poor in vivo host
environment. Existing models and analyses of M. tuberculosis
metabolic networks are able to reproduce experimentally
measured cellular growth rates and identify genes required for
growth in a range of different in vitro media. However, these
models, under in vitro conditions, do not provide an adequate
description of the metabolic processes required by the pathogen
to infect and persist in a host. RESULTS: To better account for
the metabolic activity of M. tuberculosis in the host
environment, we developed a set of procedures to systematically
modify an existing in vitro metabolic network by enhancing the
agreement between calculated and in vivo-measured gene
essentiality data. After our modifications, the new in vivo
network contained 663 genes, 838 metabolites, and 1,049
reactions and had a significantly increased sensitivity (0.81)
in predicted gene essentiality than the in vitro network
(0.31). We verified the modifications generated from the purely
computational analysis through a review of the literature and
found, for example, that, as the analysis suggested, lipids are
used as the main source for carbon metabolism and oxygen must
be available for the pathogen under in vivo conditions.
Moreover, we used the developed in vivo network to predict the
effects of double-gene deletions on M. tuberculosis growth in
the host environment, explore metabolic adaptations to life in
an acidic environment, highlight the importance of different
enzymes in the tricarboxylic acid-cycle under different
limiting nutrient conditions, investigate the effects of
inhibiting multiple reactions, and look at the importance of
both aerobic and anaerobic cellular respiration during
infection. CONCLUSIONS: The network modifications we
implemented suggest a distinctive set of metabolic conditions
and requirements faced by M. tuberculosis during host infection
compared with in vitro growth. Likewise, the double-gene
deletion calculations highlight the importance of specific
metabolic pathways used by the pathogen in the host
environment. The newly constructed network provides a
quantitative model to study the metabolism and associated drug
targets of M. tuberculosis under in vivo conditions.
This model is hosted on
BioModels Database
and identified by:
MODEL1507180018.
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2015-07-30 | MODEL1507180018 | BioModels
Project description:To survive a dynamic host environment, Mycobacterium tuberculosis must endure a series of challenges from reactive oxygen and nitrogen stress, to drastic shifts in oxygen availability. The mycobacterial Lsr2 protein has been implicated in reactive oxygen defense via direct protection of DNA. To examine the role of Lsr2 in pathogenesis and physiology of M. tuberculosis, we generated a strain deleted for lsr2. Analysis of the M. tuberculosis Δlsr2 strain demonstrated that Lsr2 is not required for DNA protection, as this strain was as equally susceptible as the wild-type to DNA-damaging agents. The lsr2 mutant did display severe growth defects under normoxic and hyperoxic conditions, but was not required for growth under low oxygen conditions. However, it was also required for adaptation to anaerobiosis. The defect in anaerobic adaptation led to a marked decrease in viability during, as well as a lag in recovery from, anaerobiosis. Gene expression profiling of Δlsr2 under aerobic and anaerobic conditions in conjunction with published DNA binding-site data indicate that Lsr2 is a global transcriptional regulator controlling adaptation to changing oxygen levels. The Δlsr2 strain was capable of establishing an early infection in the Balb/c mouse model; however, it was severely defective in persisting in the lungs and caused no discernible lung pathology. These findings demonstrate M. tuberculosis Lsr2 is a global transcriptional regulator required for control of genes involved in adaptation to extremes in oxygen availability and is required for persistent infection.
2014-05-24 | GSE57948 | GEO