Mycobacterium tuberculosis CDC1551
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ABSTRACT:
PROVIDER: PRJNA248293 | ENA |
REPOSITORIES: ENA
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Project description:The stringent response, involving the regulatory molecules inorganic polyphosphate (poly P) and (p)ppGpp, is believed to mediate Mycobacterium tuberculosis persistence. In this study, we identified a novel exopolyphosphatase responsible for poly P hydrolysis. Using two different poly P-accumulating M. tuberculosis recombinant strains, we found that increased poly P content drives the organisms into early growth arrest, and contributes to tolerance to the cell wall-active agent isoniazid, increased resistance to stress conditions, and improved survival in macrophages. Transcriptomic and metabolomics analysis revealed metabolic downshift manifested by reduced expression of the transcriptional and translational machinery, and shift from utilization of glucose as a carbon source. In summary, regulation of the poly P balance is critical for persister formation in M. tuberculosis. The transcriptome of poly P accumulation strains, Rv1026 knock-down and ppk1 knock-in were compared to empty vector strains by RNA-seq.
2015-02-20 | E-GEOD-57868 | biostudies-arrayexpress
Project description:The stringent response, involving the regulatory molecules inorganic polyphosphate (poly P) and (p)ppGpp, is believed to mediate Mycobacterium tuberculosis persistence. In this study, we identified a novel exopolyphosphatase responsible for poly P hydrolysis. Using two different poly P-accumulating M. tuberculosis recombinant strains, we found that increased poly P content drives the organisms into early growth arrest, and contributes to tolerance to the cell wall-active agent isoniazid, increased resistance to stress conditions, and improved survival in macrophages. Transcriptomic and metabolomics analysis revealed metabolic downshift manifested by reduced expression of the transcriptional and translational machinery, and shift from utilization of glucose as a carbon source. In summary, regulation of the poly P balance is critical for persister formation in M. tuberculosis.
2015-02-20 | GSE57868 | GEO
Project description:It is very important to understand the mechanisms how bacteria become tolerant towards antibiotics during clinical therapy. In a previous study we showed that increased daptomycin (DAP) tolerance of Staphylococcus aureus was due to a point mutation in pitA (inorganic phosphate transporter) that led to intracellular accumulation of both inorganic phosphate (Pi) and polyphosphate (polyP). DAP tolerance in that pitA6 mutant differs from classical resistance mechanisms as there was no increase in minimal inhibitory concentration (MIC). In this study we demonstrate that DAP tolerance in the pitA6 mutant is not triggered by the accumulation of polyP. Transcriptome analysis revealed that about 234 genes were at least 2.0-fold differently expressed in the mutant. Particularly, genes involved in protein biosynthesis, carbohydrate and lipid metabolism as well as in replication and maintenance of DNA were downregulated. However, the most important change was the upregulation of the dlt-operon, which is induced by the accumulation of intracellular Pi. The GraXRS system, known as activator of both dlt and mprF, as well as surface charge, cell wall thickness or the content of wall teichoic acids (WTA) are not involved in DAP tolerance in the pitA6 mutant. In conclusion the DAP tolerance in the pitA6 mutant is due to an upregulation of the dlt-operon triggered directly or indirectly by the accumulation of Pi. WT strain HG003 and its pitA mutant were used to compare transcriptomic changes after 6 or 8 hours of growth in suspension in TSB medium
2016-02-10 | E-GEOD-77069 | biostudies-arrayexpress
Project description:It is very important to understand the mechanisms how bacteria become tolerant towards antibiotics during clinical therapy. In a previous study we showed that increased daptomycin (DAP) tolerance of Staphylococcus aureus was due to a point mutation in pitA (inorganic phosphate transporter) that led to intracellular accumulation of both inorganic phosphate (Pi) and polyphosphate (polyP). DAP tolerance in that pitA6 mutant differs from classical resistance mechanisms as there was no increase in minimal inhibitory concentration (MIC). In this study we demonstrate that DAP tolerance in the pitA6 mutant is not triggered by the accumulation of polyP. Transcriptome analysis revealed that about 234 genes were at least 2.0-fold differently expressed in the mutant. Particularly, genes involved in protein biosynthesis, carbohydrate and lipid metabolism as well as in replication and maintenance of DNA were downregulated. However, the most important change was the upregulation of the dlt-operon, which is induced by the accumulation of intracellular Pi. The GraXRS system, known as activator of both dlt and mprF, as well as surface charge, cell wall thickness or the content of wall teichoic acids (WTA) are not involved in DAP tolerance in the pitA6 mutant. In conclusion the DAP tolerance in the pitA6 mutant is due to an upregulation of the dlt-operon triggered directly or indirectly by the accumulation of Pi.
2016-02-10 | GSE77069 | GEO
Project description:The development of antibiotic tolerance is believed to be a major factor in the lengthy duration of current tuberculosis therapies. In the current study, we have modeled antibiotic tolerance in vitro by exposing Mycobacterium tuberculosis to two distinct stress conditions: progressive hypoxia and nutrient starvation [phosphate-buffered saline (PBS)]. We then studied the bacterial transcriptional response using RNA-seq and employed a bioinformatics approach to identify important transcriptional regulators, which was facilitated by a novel Regulon Enrichment Test (RET). A total of 17 transcription factor (TF) regulons were enriched in the hypoxia gene set and 16 regulons were enriched in the nutrient starvation, with 12 regulons enriched in both conditions. Using the same approach to analyze previously published gene expression datasets, we found that three M. tuberculosis regulons (Rv0023, SigH, and Crp) were commonly induced in both stress conditions and were also among the regulons enriched in our data. These regulators are worthy of further study to determine their potential role in the development and maintenance of antibiotic tolerance in M. tuberculosis following stress exposure.
2018-04-03 | GSE104599 | GEO
Project description:Inorganic polyphosphate (Poly P) is a polymer of various phosphate residues linked by phosphoanhydride bonds as in ATP. It is found in all cells in nature with roles in the origin and survival of species, particularly in bacteria. To study the role of the inorganic polyphosphate in bacteria, we obtained knockout mutants of polyP metabolism genes in Escherichia coli K12. We performed DNA microarray experiments of single mutants in polyphosphate kinase 1 (PPK1), exopolyphosphatase (PPX) and also with the double mutant (PPK1 and PPX). The mutant strains growth normally in LB medium but have different colony morphology phenotypes. All mutants have flagellation problems and a detail description of all gain and lost phenotypes o these strains will be published soon because we performed a complete phenotypic microarray study of all three mutant strains.
2011-06-15 | GSE29954 | GEO
Project description:Understanding the roles of dksA and greA in inorganic polyphosphate accumulation in Escherichia coli
| PRJNA604995 | ENA
Project description:In Mycobacterium tuberculosis, the efflux pump, EfpA, plays an essential but uncharacterised role in its physiology and antibiotic tolerance. In this study, an ATc-inducible CRISPR interference (CRISPRi) system was introduced into M. tuberculosis to knock-down the expression of efpA and determine any subsequent effects on the organism. As part of the study, microarray experiments were performed to determine any changes in gene expression caused by efpA repression M. tuberculosis by comparing the transcriptomic profile between ATc-induced efpA knock-down cultures to that of efpA knock-down cultures without ATc-induction.
2024-06-19 | E-MTAB-13755 | biostudies-arrayexpress
Project description:Detailed methods and results are included in our published manuscript titled "Mitochondrial Inorganic Polyphosphate is Required to Maintain Proteostasis Within the Organelle".
2024-06-27 | MSV000095168 | MassIVE
Project description:Causative agent of tuberculosis.
| PRJNA223 | ENA