Project description:This SuperSeries is composed of the following subset Series: GSE36341: mRNA degradation in Mycobacterium tuberculosis under aerobic conditions GSE36342: mRNA degradation in Mycobacterium smegmatis under aerobic conditions GSE36343: mRNA degradation in Mycobacterium tuberculosis during cold and hypoxic stress GSE36344: mRNA degradation in Mycobacterium tuberculosis with DosR ectopically induced Refer to individual Series
Project description:Introduction: Tuberculosis (TB) is a serious human disease caused by the bacterium Mycobacterium tuberculosis (Mtb). One third of the world’s population is estimated to be latently infected with Mtb. Exact mechanisms and properties of latent TB infection (LTBI) are not fully elucidated. In essence, the pathogen can enter a dormant or latent state characterized by limited growth and metabolism, resulting in absence of clinical symptoms in the host, and most importantly by increased phenotypic tolerance to the commonly used medications, thereby allowing indefinite persistence in the human body. This persistence is the main reason why the current treatment of new-onset pulmonary TB is very long, consisting of a six months therapy of four antibiotics (rifampicin, isoniazid, pyrazinamide, and ethambutol for the first two months, and only rifampicin and isoniazid for the last four months). Current state of the art: To fight TB globally and more efficiently, it is essential to shorten the treatment for TB with new drugs that are efficient also against LTBI. To facilitate discovery of such drugs, in vitro models for LTBI can be used for high throughput screening of chemical libraries. Current in vitro models such as nutrient starvation (Betts et al. 2002), nutrient depletion (Hampshire et al. 2004; Rifat, Bishai, and Karakousis 2009), progressive hypoxia (Wayne and Hayes 1996), nitric oxide treatment (Martin I. Voskuil et al. 2003) and multiple stress (Deb et al. 2009) mimic the dormant state of Mtb, but the technical settings and equipment required for these models obstruct high throughput applications. Proposed model: The streptomycin (STR)-starved 18b model (SS18b) is a simple and drug discovery efficient Mtb latency model successfully applicable to both in vitro and in vivo settings (Zhang et al. 2012). It is based on the Mtb strain 18b, which is a STR-dependent mutant that enters a viable but nonreplicating state in the absence of STR (Hashimoto 1955). Despite the successful model, we know very little about 18b. How well does SS18b mimic the bacterial response to the complex host-pathogen interactions underlying LTBI, and how does the SS18b response compare to that of other dormancy models are still open questions. In this work we analyse the complete genome of 18b and describe the transcriptomic response of 18b to STR depletion. 12 samples were analyzed. Four biological replicates were sampled during the exponential growth phase, in presence of streptomycin. Four biological replicates derived after 2 weeks of streptomycin depletion, and two biological replicates derive after 4 weeks of streptomycin depletion. Two replicates derive from the resubmission of streptomycin after four weeks of depletion.
Project description:This SuperSeries is composed of the following subset Series: GSE34919: Genome-wide Definition of the SigF Regulon in Mycobacterium tuberculosis (ChIP-chip) GSE34922: Genome-wide Definition of the SigF Regulon in Mycobacterium tuberculosis (Expression) Refer to individual Series
Project description:This SuperSeries is composed of the following subset Series: GSE6209: The global transcriptional profile of Mycobacterium tuberculosis during human macrophages infection GSE7962: Sigma factor E of Mycobacterium tuberculosis controls the expression of bacterial components that modulate macrophages Keywords: SuperSeries Refer to individual Series
Project description:Comparison of gene expression profile of the whiB4 mutant strain of Mycobacterium tuberculosis with the wild type Mycobacterium tuberculosis H37RV Mtb WhiB4 mutant mRNA was compared with the mRNA of wtMtb H37RV under aerobic conditons Aerbic conditions OD600 nm of 0.4, MtbWhiB4KO vs wtMtb, biological replicates: 3 wt Mtb H37RV and 3 MtbWhiB4 KO
Project description:In other bacteria, arginine induces the expression of genes involved in arginine catabolism. This study obtained the identification of genes involved in the arginine metabolism of Mycobacterium tuberculosis. Mycobacterium tuberculosis was cultured with arginine or ammonium chloride as sole nitrogen source. In the log phase of growth, RNA was isolated and whole genome expression was determined. The study contains three biological replicates.
Project description:Beste2007 - Genome-scale metabolic network of
Mycobacterium tuberculosis (GSMN_TB)
This model is described in the article:
GSMN-TB: a web-based
genome-scale network model of Mycobacterium tuberculosis
Beste DJ, Hooper T, Stewart G, Bonde
B, Avignone-Rossa C, Bushell ME, Wheeler P, Klamt S, Kierzek AM,
Genome Biol. 2007; 8(5): R89
BACKGROUND: An impediment to the rational development of
novel drugs against tuberculosis (TB) is a general paucity of
knowledge concerning the metabolism of Mycobacterium
tuberculosis, particularly during infection. Constraint-based
modeling provides a novel approach to investigating microbial
metabolism but has not yet been applied to genome-scale
modeling of M. tuberculosis. RESULTS: GSMN-TB, a genome-scale
metabolic model of M. tuberculosis, was constructed, consisting
of 849 unique reactions and 739 metabolites, and involving 726
genes. The model was calibrated by growing Mycobacterium bovis
bacille Calmette Guérin in continuous culture and
steady-state growth parameters were measured. Flux balance
analysis was used to calculate substrate consumption rates,
which were shown to correspond closely to experimentally
determined values. Predictions of gene essentiality were also
made by flux balance analysis simulation and were compared with
global mutagenesis data for M. tuberculosis grown in vitro. A
prediction accuracy of 78% was achieved. Known drug targets
were predicted to be essential by the model. The model
demonstrated a potential role for the enzyme isocitrate lyase
during the slow growth of mycobacteria, and this hypothesis was
experimentally verified. An interactive web-based version of
the model is available. CONCLUSION: The GSMN-TB model
successfully simulated many of the growth properties of M.
tuberculosis. The model provides a means to examine the
metabolic flexibility of bacteria and predict the phenotype of
mutants, and it highlights previously unexplored features of M.
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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) Overall design: 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.
Project description:Transcriptional profiling of Mycobacterium tuberculosis H37Rv strains comparing control DMSO treated strains with Lupulone treated strains. Goal was to determine the effects of Lupulone against Mycobacterium tuberculosis H37Rv strains. Overall design: Two-condition experiment,control DMSO treated strains vs. Lupulone treated strains. Biological replicates: 2 control replicates, 2 Lupulone replicates.
Project description:The new microarray described for Mycobacterium tuberculosis in our study has a more complete reprensentation of the genome than any other array design reported till date. Further, protocols for sample preparation, labelling and hybridisation for accurate gene expression profiling of M.tuberculosis have been optimised. Whole genome expression profiling on Mycobacterium tuberculosis H37Rv (OD600 0.4-0.5) was performed using exponential phase cultures after 0 and 6 Hrs in presence and absence of drug (Isoniazid) by using PolyA-dT and WT method. The exponential culture after 24 and 72 Hrs were used for validating the specific hybridization with or without formamide. All time points had two biological replicates with two technical replicates.