Sulfur metabolism in Mycobacterium tuberculosis
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB64040 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR11648675_1.fastq.gz | Fastqsanger.gz | |||
| ERR11648675_2.fastq.gz | Fastqsanger.gz | |||
| ERR11648576_1.fastq.gz | Fastqsanger.gz | |||
| ERR11648576_2.fastq.gz | Fastqsanger.gz | |||
| ERR11648678_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:Tuberculosis (TB) is currently the number one killer among infectious diseases worldwide. Lipids are abundant molecules during the infectious cycle of Mycobacterium tuberculosis (Mtb) and studies better mimicking its actual metabolic state during pathogenesis are needed. Though most studies have focused on the mycobacterial lipid metabolism under standard conditions (carbon source, drugs, stress), little is known about the transcriptome of Mtb in a lipid environment. Here we determine the transcriptome of Mtb H37Rv in a lipid-rich environment (mixture of cholesterol, palmitic, stearic and oleic acids), under aerobic and hypoxic conditions, using RNAseq technology. Lipids significantly induced the expression of 368 genes. A main core lipid response was observed involving efflux systems, iron caption and sulfur reduction. In co-expression with ncRNAs and other genes discussed below, may act coordinately to prepare the machinery conferring drug tolerance and increasing a persistent population. Our findings could be useful to tag relevant pathways for the development of new drugs, vaccines and new strategies to control TB.
2018-01-12 | GSE100097 | GEO
Project description:H2S is a potent gasotransmitter in eukaryotes and bacteria. Host-derived H2S was shown to profoundly alter M. tuberculosis (Mtb) energy metabolism and growth. However, compelling evidence for endogenous production of H2S and its role in Mtb physiology is lacking. We show that multi-drug-resistant and drug-susceptible clinical Mtb strains produce H2S, whereas H2S production in non-pathogenic M. smegmatis is barely detectable. We identified Rv3684 (Cds1) as an H2S-producing enzyme in Mtb and show that cds1 disruption reduces, but does not eliminate H2S production, suggesting the involvement of multiple genes in H2S production. We identified endogenous H2S to be an effector molecule that maintains bioenergetic homeostasis by regulating respiration. Importantly, H2S plays a key role in central metabolism by modulating the balance between oxidative phosphorylation and glycolysis, and functions as a sink to recycle sulfur atoms back to cysteine to maintain sulfur homeostasis. Lastly, Mtb-generated H2S regulates redox homeostasis and susceptibility to the anti-TB drugs clofazimine and rifampicin. These findings reveal previously unknown facets of Mtb physiology and have implications for routine laboratory culturing, understanding drug susceptibility, and improved diagnostics.
2021-08-16 | PXD022969 | Pride
Project description:Mycobacterium tuberculosis (Mtb) has evolved into a highly successful human pathogen. It deftly subverts the bactericidal mechanisms of alveolar macrophages, ultimately inducing granuloma formation and establishing long-term residence in the host. These hallmarks of Mtb infection are facilitated by the metabolic adaptation of the pathogen to its surrounding environment and the biosynthesis of molecules that mediate its interactions with host immune cells. The sulfate assimilation pathway of Mtb produces a number of sulfur-containing metabolites with important contributions to pathogenesis and survival. This pathway is regulated by diverse environmental cues and regulatory proteins that mediate sulfur transactions in the cell. Here, we discuss the transcriptional and biochemical mechanisms of sulfur metabolism regulation in Mtb and potential small molecule regulators of the sulfate assimilation pathway that are collectively poised to aid this intracellular pathogen in its expert manipulation of the host. From this global analysis, we have identified a subset of sulfur-metabolizing enzymes that are sensitive to multiple regulatory cues and may be strong candidates for therapeutic intervention.
| S-EPMC3141025 | biostudies-other
Project description:Spaceflight induces hepatic damage, partially owing to oxidative stress caused by the space environment such as microgravity and space radiation. We examined the roles of anti-oxidative sulfur-containing compounds on hepatic damage after spaceflight. We analyzed the livers of mice on board the International Space Station for 30 days. During spaceflight, half of the mice were exposed to artificial earth gravity (1 g) using centrifugation cages. Sulfur-metabolomics of the livers of mice after spaceflight revealed a decrease in sulfur antioxidants (ergothioneine, glutathione, cysteine, taurine, thiamine, etc.) and their intermediates (cysteine sulfonic acid, hercynine, N-acethylserine, serine, etc.) compared to the controls on the ground. Furthermore, RNA-sequencing showed upregulation of gene sets related to oxidative stress and sulfur metabolism, and downregulation of gene sets related to glutathione reducibility in the livers of mice after spaceflight, compared to controls on the ground. These changes were partially mitigated by exposure to 1 g centrifugation. For the first time, we observed a decrease in sulfur antioxidants based on a comprehensive analysis of the livers of mice after spaceflight. Our data suggest that a decrease in sulfur-containing compounds owing to both microgravity and other spaceflight environments (radiation and stressors) contributes to liver damage after spaceflight.
2023-08-14 | GSE240751 | GEO
Project description:The batch fermentation of Clostridium acetobutylicum is characterized by an acetogenic growth phase during exponential growth when mainly acetate and butyrate are fermentation products. Then, at the end of exponential growth and during stationary phase, the organism switches to solventogenic growth and large amounts of acetone, ethanol and butanol are produced. These growth phases can be studied independent from each other in a phosphate-limited continuous culture. In transcription analysis of continuous cultures using DNA microarrays it became evident that, among others, operons involved in sulfur assimilation are strongly up-regulated during solventogenesis. Using the ClosTron technique we constructed two knock-out mutants in the genes CAC0105 and CAC0930 annotated as involved in sulfate reduction and cysteine biosynthesis. Complementation experiments were carried out with sulfite and cysteine to prove the predicted function. The fermentation experiments of wild type and mutants using phosphate-limited and sulfur-limited continuous culture demonstrated that less sulfur source was consumed in solventogenic phase and the efficiency of cysteine uptake became lower. DNA microarrays were performed to study the difference of transcriptional expression when the wild type was challenged with insufficient sulfur source and the mccB (CAC0930) mutant was inactivated in the continuous culture. The result provided insights into understanding the sulfur metabolism regulatory.
2015-04-15 | E-MTAB-2745 | biostudies-arrayexpress
Project description:Mutations in the cysB, sconB and sconC genes affect sulfur metabolism in Aspergillus nidulans in different ways. Mutation of cysB blocks synthesis of cysteine by the main pathway leaving only the less effective alternative route. Mutations of sconB or sconC affect subunits of the SCF ubiquitin ligase complex, a negative controller of METR transcription factor, resulting in specific activation of a number of sulfur assimilation and metabolism genes, ultimately leading to elevated levels of cysteine and glutathione in scon mutants. We compared transcriptomes of these three mutants with that of a wild type strain finding that expression of a few hundred genes is altered at least twofold indicating a major reorganization of cellular metabolism. Despite the different effects of the cysB and scon mutations on sulfur metabolism they affect expression of overlapping sets of genes. We identified categories of the Functional Catalogue assigned to the differentially expressed genes and selected categories most enriched among the up- and down-regulated gene groups. Besides those involved in sulfur metabolism, many up-regulated genes are related to stress responses. The two-component signal transduction system is most enriched in genes up-regulated in the cysB, sconB and sconC mutants. This category contains histidine kinases that sense and transduce environmental signals to a cascade of protein kinases. Genes encoding heat shock proteins are also up-regulated, as are genes of the glutamate degradation pathway. The latter, also known as the GABA shunt, is induced by oxidative stress. A large group of up-regulated genes are involved in carbohydrate and energy metabolism, including genes coding for enzymes of trehalose and glycerol synthesis. Genes coding for enzymes of alcohol fermentation, which are induced in response to anaerobic stress, are also up-regulated in the mutants studied. The altered expression of the carbohydrate metabolism genes is accompanied by changes in sugar accumulation in mycelia and conidia of the mutants. Among the down-regulated genes the most numerous are those encoding membrane proteins and enzymes involved in secondary metabolism, including the penicillin biosynthesis cluster. Genes coding for lysozyme are down-regulated too. As secondary metabolites often inhibit growth of other organisms, lowered expression of genes responsible for their synthesis suggests a decreased response to biotic stress in the mutants studied. Comparison of transcriptomes of the filamentous fungus Aspergillus nidulans strains bearing mutations in the cysB, sconB or sconC genes, affecting sulfur metabolism in different ways, with that of the wild type (WT) strain. Three biological replicates of WT vs cysB and WT vs sconC comparisons were performed and four biological replicates of WT vs sconB comparison were done. Each biological replicate had two technical replicates with dye swapping. A total of twenty individual hybridizations were made.
2014-02-14 | E-GEOD-54130 | biostudies-arrayexpress
Project description:Mutations in the cysB, sconB and sconC genes affect sulfur metabolism in Aspergillus nidulans in different ways. Mutation of cysB blocks synthesis of cysteine by the main pathway leaving only the less effective alternative route. Mutations of sconB or sconC affect subunits of the SCF ubiquitin ligase complex, a negative controller of METR transcription factor, resulting in specific activation of a number of sulfur assimilation and metabolism genes, ultimately leading to elevated levels of cysteine and glutathione in scon mutants. We compared transcriptomes of these three mutants with that of a wild type strain finding that expression of a few hundred genes is altered at least twofold indicating a major reorganization of cellular metabolism. Despite the different effects of the cysB and scon mutations on sulfur metabolism they affect expression of overlapping sets of genes. We identified categories of the Functional Catalogue assigned to the differentially expressed genes and selected categories most enriched among the up- and down-regulated gene groups. Besides those involved in sulfur metabolism, many up-regulated genes are related to stress responses. The two-component signal transduction system is most enriched in genes up-regulated in the cysB, sconB and sconC mutants. This category contains histidine kinases that sense and transduce environmental signals to a cascade of protein kinases. Genes encoding heat shock proteins are also up-regulated, as are genes of the glutamate degradation pathway. The latter, also known as the GABA shunt, is induced by oxidative stress. A large group of up-regulated genes are involved in carbohydrate and energy metabolism, including genes coding for enzymes of trehalose and glycerol synthesis. Genes coding for enzymes of alcohol fermentation, which are induced in response to anaerobic stress, are also up-regulated in the mutants studied. The altered expression of the carbohydrate metabolism genes is accompanied by changes in sugar accumulation in mycelia and conidia of the mutants. Among the down-regulated genes the most numerous are those encoding membrane proteins and enzymes involved in secondary metabolism, including the penicillin biosynthesis cluster. Genes coding for lysozyme are down-regulated too. As secondary metabolites often inhibit growth of other organisms, lowered expression of genes responsible for their synthesis suggests a decreased response to biotic stress in the mutants studied.
2014-02-14 | GSE54130 | GEO
Project description:Desulfurella amilsii is an acidotolerant sulfur-reducing bacterium isolated from sediments of an acidic river. It can grow in a broad range of pH and can obtain energy via respiring elemental sulfur or thiosulfate, as well as by disproportionating elemental sulfur. Its genome encodes the enzyme sulfur reductase, and several rhodanese-like proteins, possibly playing a role in sulfur respiration and disproportionation. Thiosulfate reductase and dissimilatory sulfite reductase are encoded and might play a role during the respiration of thiosulfate. The involvement of these enzymes in the reductive routes of sulfur metabolism is not yet clearly understood. Desulfurella amilsii was used in this study to combine strategies for sulfur metabolism research on the protein level to shed some light on the pathways involved in the metabolism of this microorganism.
2018-10-19 | PXD008496 | Pride
Project description:The Chlamydomonas reinhardtii transcriptome was characterized from nutrient-replete and sulfur-depleted wild-type and snrk2.1 mutant cells; the mutant is null for the regulatory serine-threonine kinase SNRK2.1, which is required for acclimation to sulfur deprivation. The transcriptome analyses involved microarray hybridization and RNA-seq technology; RT-qPCR evaluation of the data obtained by these techniques showed that RNA-seq is significantly more quantitative than microarray hybridizations. Sulfur-deprivation-responsive transcripts included those encoding proteins involved in sulfur acquisition and assimilation, recycling of sulfur-containing amino acids, synthesis of reduced sulfur metabolites and cofactors, and modification of cellular structures such as the cell wall and complexes associated with the photosynthetic apparatus. Moreover, the data suggest that cells deprived of sulfur favors accumulation of proteins with fewer sulfur-containing amino acids. Most of these sulfur-deprivation responses are controlled by the SNRK2.1 kinase. Furthermore, the snrk2.1 mutant exhibits a set of unique responses during both sulfur-replete and sulfur-depleted conditions that are not observed in wild-type cells. Many of these responses are likely to be elicited by singlet O2 accumulation in the mutant cells. The transcriptome results for the wild-type and mutant cells strongly suggest the occurrence of massive changes in cellular physiology and metabolism as the cells become depleted for sulfur, and reveal aspects of acclimation that are likely critical for cell survival. The three supplementary files GSE17970_supplemental_table_*.xls below include results of the differential expression analysis (expression estimates, fold changes and p-values), and different clusters of functionally related genes.
2010-07-08 | GSE17970 | GEO
Project description:The purple sulfur bacterium Allochromatium vinosum DSM 180T is one of the best studied sulfur-oxidizing anoxygenic phototrophic bacteria and has been developed into a model organism for laboratory-based studies of oxidative sulfur metabolism. Here, we took advantage of the organism’s high metabolic versatility and performed whole-genome transcriptional profiling to investigate the response of A. vinosum cells upon exposure to sulfide, thiosulfate, elemental sulfur or sulfite as compared to photoorganoheterotrophic growth on malate. Differential expression (at least twofold) of 1149 genes was observed, corresponding to 30% of the A. vinosum genome. A total of 549 genes were identified for which relative transcription increased at least twofold during growth on one of the different sulfur sources while relative transcription of 599 genes decreased. A significant number of genes that were strongly induced have documented sulfur-metabolism-related functions. Among these are the dsr genes including dsrAB for dissimilatory sulfite reductase and the sgp genes for the proteins of the sulfur globule envelope thus confirming former results. In addition we were able to identify new genes encoding proteins with appropriate subcellular localization and properties to participate in oxidative dissimilatory sulfur metabolism. Two of these were chosen for inactivation and phenotypic analyses of the respective mutant strains. This approach verified the importance of the encoded proteins for the oxidation of sulfide and thereby also documented the suitability of comparative transcriptomics for the identification of new sulfur-related genes in anoxygenic phototrophic sulfur bacteria.
2013-07-29 | GSE44041 | GEO