Chemical disarming of isoniazid resistance in Mycobacterium tuberculosis
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ABSTRACT:
PROVIDER: PRJNA532912 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Transcriptional profiling of Mycobacterium tuberculosis mc2 7000 surviving 4 days of isoniazid treatment relative to untreated to investigate genes relevant to survival in genotypically isoniazid-sensitive cells
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Project description:Transcriptional profiling of Mycobacterium tuberculosis H37Rv after 4 hours of combination isoniazid and cysteine treatment relative to treatment with isoniazid alone.
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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.
2013-06-01 | E-GEOD-45811 | biostudies-arrayexpress
Project description:In order to study the effect of manganese on the immunity of macrophages, we established a model of infection with Mycobacterium tuberculosis and treated it with manganese and isoniazid for 12 hours
2022-08-26 | GSE211666 | GEO
Project description:Tuberculosis (TB) is one of the deadliest infectious disorders in the world. To effectively TB manage, an essential step is to gain insight into the lineage of Mycobacterium tuberculosis (MTB) strains and the distribution of drug resistance. Although the Campania region is declared a cluster area for the infection, to contribute to the effort to understand TB evolution and transmission, still poorly known, we have generated a dataset of 159 genomes of MTB strains, from Campania region collected during 2018-2021, obtained from the analysis of whole genome sequence data. The results show that the most frequent MTB lineage is the 4 according for 129 strains (81.11%). Regarding drug resistance, 139 strains (87.4%) were classified as multi susceptible, while the remaining 20 (12.58%) showed drug resistance. Among the drug-resistance strains, 8 were isoniazid-resistant MTB (HR-MTB), 7 were resistant only to one antibiotic (3 were resistant only to ethambutol and 3 isolate to streptomycin while one isolate showed resistance to fluoroquinolones), 4 multidrug-resistant MTB, while only one was classified as pre-extensively drug-resistant MTB (pre-XDR). This dataset expands the existing available knowledge on drug resistance and evolution of MTB, contributing to further TB-related genomics studies to improve the management of TB infection.
2023-11-17 | E-MTAB-13058 | biostudies-arrayexpress
Project description:The ability of Mycobacterium tuberculosis (Mtb) to adopt heterogeneous physiological states, underlies it’s success in evading the immune system and tolerating antibiotic killing. Drug tolerant phenotypes are a major reason why the tuberculosis (TB) mortality rate is so high, with over 1.8 million deaths annually. To develop new TB therapeutics that better treat the infection (faster and more completely), a systems-level approach is needed to reveal the complexity of network-based adaptations of Mtb. Here, we report the transcriptional response of Mtb to the drug isoniazid. We performed transcriptomic sequencing (RNA-seq) on Mtb bacilli at 4, 24, 72 h following exposure to the drug.
2021-12-15 | GSE165581 | GEO
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:This project describes the isoniazid (INH) resistance acquisition event in Mycobacterium tuberculosis (Mtb) from the proteomics perspective. In this way, an exploration of the protein differences, comparing clonal INH susceptible (INHs) and INHr pairs of Mtb were evaluated. One clonal clinical and one clonal laboratory-derived Mtb pair with different susceptibility profiles to INH were studied. The laboratory INHr strain had one katG mutation (V1A), while the clinical INHr strain had two (V1A and E3V). Large-scale bacterial cultures were grown in triplicate to obtain secreted proteins as well as proteins from cell fractions. The resulting peptide solutions from all fractions were analyzed using liquid-chromatography coupled with tandem mass spectrometry (LC-MS/MS). LC-MS/MS spectra were compared against an Mtb database to determine the protein abundance. Protein abundance differences were tested by Student’s t test. Looking at the same cellular fractions, there were 25 commonly altered Mtb proteins after acquiring INH resistance. These proteins were involved in ATP synthase machinery, lipid metabolism, regulatory events, virulence, detoxification and adaptation processes.
2018-06-25 | PXD009549 | Pride
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:Out of the 10 million of tuberculosis (TB) cases estimated in the world, around 14% are isoniazid (INH) resistant among new cases and 29% among previously treated cases in the last decade. INH is one of the oldest but also one of the more potent drugs to eliminate Mycobacterium tuberculosis (Mtb), the causing agent of TB. Because of the efficiency of isoniazid (INH) against Mycobacterium tuberculosis (Mtb), many studies are still focused in better understand its role in different bacterial metabolic pathways. We recently conducted a study that evaluated the changes in the protein abundance at different cellular fractions when clonal strains of Mtb developed INH resistance in the clinical and laboratory setting. Here, we want to establish which of the protein changes occurred or started because of the initial exposure to INH. Additionally, we wanted to evaluate if those changes happen differently in strains that are sensitive or resistant to INH, evaluating different cellular compartments from two different genetic lineages of Mtb. For this purpose, we analyzed the proteome of each cellular compartment (cytosol, cell wall, membrane and secreted proteins) through liquid chromatography (nano-HPLC) coupled to mass spectrometry using the Orbitrap Velos instrument and a t-test to perform the statistical analysis for each pair comparison.
2019-06-17 | PXD007588 | Pride