Ontology highlight
ABSTRACT:
PROVIDER: PRJNA600079 | ENA |
REPOSITORIES: ENA
Similar Datasets
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:Transcriptional profiling of mycobacterium tuberculosis clinical isolates in China comparing extensively drug-resistant tuberculosis with drug sensitive one. The same condition experiment. The samples were from the different drug-resistant strains. Only one replicate.
2009-04-04 | E-GEOD-15540 | biostudies-arrayexpress
Project description:The emergence of drug resistance among tuberculosis (TB) patients is often associated with their non-compliance to the length of the chemotherapy, which can reach up to 2 years for the treatment of multi-drug-resistant (MDR) TB. Drugs that would kill TB faster and would not lead to the development of drug resistance could shorten chemotherapy significantly. In Escherichia coli, the common mechanism of cell death by bactericidal antibiotics is the generation of highly reactive hydroxyl radicals via the Fenton reaction. Since ascorbic acid (vitamin C) is known to drive the Fenton reaction, we tested whether the Fenton reaction could lead to a bactericidal event in Mycobacterium tuberculosis by treating M. tuberculosis cultures with vitamin C. Here, we report that the addition of vitamin C to drug-susceptible, MDR and extensively drug-resistant (XDR) M. tuberculosis strains results in sterilization of the cultures in vitro. We show that the sterilizing effect of vitamin C on M. tuberculosis was dependent on the production of high ferrous ion levels and reactive oxygen species. Although, this potent sterilizing activity of vitamin C against M. tuberculosis in vitro was not observed in mice, we believe this activity needs further investigation. Comparison of vitamin C treated Mycobacterium tuberculosis transcriptome relative to untreated; Three biological replicates, second is a dye flip
2013-05-24 | E-GEOD-42293 | biostudies-arrayexpress
Project description:Jamshidi2007 - Genome-scale metabolic network
of Mycobacterium tuberculosis (iNJ661)
This model is described in the article:
Investigating the metabolic
capabilities of Mycobacterium tuberculosis H37Rv using the in
silico strain iNJ661 and proposing alternative drug
targets.
Jamshidi N, Palsson BØ.
BMC Syst Biol 2007; 1: 26
Abstract:
BACKGROUND: Mycobacterium tuberculosis continues to be a
major pathogen in the third world, killing almost 2 million
people a year by the most recent estimates. Even in
industrialized countries, the emergence of multi-drug resistant
(MDR) strains of tuberculosis hails the need to develop
additional medications for treatment. Many of the drugs used
for treatment of tuberculosis target metabolic enzymes.
Genome-scale models can be used for analysis, discovery, and as
hypothesis generating tools, which will hopefully assist the
rational drug development process. These models need to be able
to assimilate data from large datasets and analyze them.
RESULTS: We completed a bottom up reconstruction of the
metabolic network of Mycobacterium tuberculosis H37Rv. This
functional in silico bacterium, iNJ661, contains 661 genes and
939 reactions and can produce many of the complex compounds
characteristic to tuberculosis, such as mycolic acids and
mycocerosates. We grew this bacterium in silico on various
media, analyzed the model in the context of multiple
high-throughput data sets, and finally we analyzed the network
in an 'unbiased' manner by calculating the Hard Coupled
Reaction (HCR) sets, groups of reactions that are forced to
operate in unison due to mass conservation and connectivity
constraints. CONCLUSION: Although we observed growth rates
comparable to experimental observations (doubling times ranging
from about 12 to 24 hours) in different media, comparisons of
gene essentiality with experimental data were less encouraging
(generally about 55%). The reasons for the often conflicting
results were multi-fold, including gene expression variability
under different conditions and lack of complete biological
knowledge. Some of the inconsistencies between in vitro and in
silico or in vivo and in silico results highlight specific loci
that are worth further experimental investigations. Finally, by
considering the HCR sets in the context of known drug targets
for tuberculosis treatment we proposed new alternative, but
equivalent drug targets.
This model is hosted on
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2015-07-30 | MODEL1507180001 | BioModels
Project description:Currently available model organisms such as Mycobacterium smegmatis and Mycobacterium bovis Bacillus Calmette-Guérin (BCG) have significantly contributed to our understanding of tuberculosis (TB) biology, these models have limitations such as differences in genome size, growth rates and virulence. Attenuated Mycobacterium tuberculosis strains may provide more representative, safer models to study M. tuberculosis biology. For example, the M. tuberculosis ΔleuDΔpanCD double auxotroph, has undergone rigorous in vitro and in vivo safety testing. Like other auxotrophic strains, this has subsequently been approved for use in biosafety level (BSL) 2 facilities. Auxotrophic strains have been assessed as models for drug-resistant M. tuberculosis and for studying latent TB. These offer the potential as safe and useful models, but it is important to understand how well these recapitulate salient features of non-attenuated M. tuberculosis. We therefore performed a comprehensive comparison of M. tuberculosis H37Rv and M. tuberculosis ΔleuDΔpanCD. These strains demonstrated similar in vitro and intra-macrophage replication rates, similar responses to anti-TB agents and whole genome sequence conservation. Shotgun proteomics analysis suggested that M. tuberculosis ΔleuDΔpanCD has an increased propensity to enter a dormant state during acid stress, which has been verified using a dual-fluorescent replication reporter assay. Importantly, infection of human peripheral blood mononuclear cells with the 2 strains elicited comparable cytokine production, demonstrating the suitability of M. tuberculosis ΔleuDΔpanCD for immunological assays. We provide comprehensive evidence to support the judicious use of M. tuberculosis ΔleuDΔpanCD as a safe and suitable model organism for M. tuberculosis research, without the need for a BSL3 facility.
2019-07-30 | PXD013677 | Pride
Project description:The alarming rise of antimicrobial resistance in Mycobacterium tuberculosis coupled with the shortage of new antibiotics has made tuberculosis (TB) control a global health priority. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the growth of multi-drug resistant isolates of M. tuberculosis. Repurposing NSAIDs, with known clinical properties and safety records, offers a direct route to clinical trials. Therefore we investigated the novel mechanisms of anti-mycobacterial action of the NSAID, carprofen. Integrative molecular and microbiological approaches revealed that carprofen, a bactericidal drug, inhibited bacterial drug efflux mechanisms. In addition, carprofen restricted mycobacterial biofilm-like growth, highlighting the requirement of efflux-mediated communicative systems for the formation of biofilms. Transcriptome profiling revealed that carprofen likely acts by inhibiting respiration through the disruption of membrane potential, which may explain why spontaneous drug-resistant mutants could not be raised due to the pleiotropic nature of carprofen’s anti-tubercular action. This immunomodulatory drug has the potential to reverse TB antimicrobial resistance by inhibiting drug efflux pumps and biofilm formation, and paves a new chemotherapeutic path for tackling tuberculosis.
2020-08-15 | E-MTAB-6191 | biostudies-arrayexpress
Project description:Transcriptional profiling of mycobacterium tuberculosis clinical isolates in China comparing extensively drug-resistant tuberculosis with drug sensitive one.
2009-04-04 | GSE15540 | GEO
Project description:The emergence of drug resistance among tuberculosis (TB) patients is often associated with their non-compliance to the length of the chemotherapy, which can reach up to 2 years for the treatment of multi-drug-resistant (MDR) TB. Drugs that would kill TB faster and would not lead to the development of drug resistance could shorten chemotherapy significantly. In Escherichia coli, the common mechanism of cell death by bactericidal antibiotics is the generation of highly reactive hydroxyl radicals via the Fenton reaction. Since ascorbic acid (vitamin C) is known to drive the Fenton reaction, we tested whether the Fenton reaction could lead to a bactericidal event in Mycobacterium tuberculosis by treating M. tuberculosis cultures with vitamin C. Here, we report that the addition of vitamin C to drug-susceptible, MDR and extensively drug-resistant (XDR) M. tuberculosis strains results in sterilization of the cultures in vitro. We show that the sterilizing effect of vitamin C on M. tuberculosis was dependent on the production of high ferrous ion levels and reactive oxygen species. Although, this potent sterilizing activity of vitamin C against M. tuberculosis in vitro was not observed in mice, we believe this activity needs further investigation.
2013-05-24 | GSE42293 | GEO