Host specificity and pathogenic mycobacteria
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB23469 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR2298720_1.fastq.gz | Fastqsanger.gz | |||
| ERR2298720_2.fastq.gz | Fastqsanger.gz | |||
| ERR2298730_1.fastq.gz | Fastqsanger.gz | |||
| ERR2298730_2.fastq.gz | Fastqsanger.gz | |||
| ERR2298740_1.fastq.gz | Fastqsanger.gz |
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Project description:Mycobacteria can synthesize NAD+ using either the de novo biosynthesis pathway or the salvage pathway. The deletion of the three genes involved specifically in the NAD+ de novo biosynthesis pathway in the human pathogen Mycobacterium tuberculosis had no effect on the growth of the strain in vivo. In contrast, the same deletion in the bovine pathogen Mycobacterium bovis resulted in a strain that could not grow in vivo and could only grow in vitro with substantial nicotinamide supplmentation. This striking difference was attributed to the known defect in the nicotinamidase PncA of M. bovis, since introducing the M. tuberculosis pncA gene into the M. bovis strain defective for de novo NAD+ biosynthesis restored growth in vitro and in vivo. This study demonstrates that NAD+ starvation is a cidal event in mycobacteria and confirms that enzymes common to the de novo and salvage pathways may be good drug targets. We also propose that simultaneously targeting both the salvage and the de novo NAD+ biosynthesis pathways represents a potentially effective way to treat infection with tubercle bacilli. To characterize the lethality induced by nicotinamide starvation transcriptional profiling of the auxotrophs was performed. Triplicate 50 mL cultures of M. tuberculosis and M. bovis Delta nadABC mutants were grown in 7H9 OADC glycerol 0.05% tween broth in 500 mL roller bottles to an OD600nm= 0.1 in a roller incubator at 37°C. The cells were washed 1x in PBS and resuspended in 50 mL 7H9 OADC glycerol 0.05% tween broth with or without 20mg/L nicotinamide and returned to the incubator. After 7 days, cultures were harvested. Three biological replicates of each of two species with one dye-flip each
2010-05-14 | E-GEOD-18909 | biostudies-arrayexpress
Project description:Mycobacteria can synthesize NAD+ using either the de novo biosynthesis pathway or the salvage pathway. The deletion of the three genes involved specifically in the NAD+ de novo biosynthesis pathway in the human pathogen Mycobacterium tuberculosis had no effect on the growth of the strain in vivo. In contrast, the same deletion in the bovine pathogen Mycobacterium bovis resulted in a strain that could not grow in vivo and could only grow in vitro with substantial nicotinamide supplmentation. This striking difference was attributed to the known defect in the nicotinamidase PncA of M. bovis, since introducing the M. tuberculosis pncA gene into the M. bovis strain defective for de novo NAD+ biosynthesis restored growth in vitro and in vivo. This study demonstrates that NAD+ starvation is a cidal event in mycobacteria and confirms that enzymes common to the de novo and salvage pathways may be good drug targets. We also propose that simultaneously targeting both the salvage and the de novo NAD+ biosynthesis pathways represents a potentially effective way to treat infection with tubercle bacilli. To characterize the lethality induced by nicotinamide starvation transcriptional profiling of the auxotrophs was performed. Triplicate 50 mL cultures of M. tuberculosis and M. bovis Delta nadABC mutants were grown in 7H9 OADC glycerol 0.05% tween broth in 500 mL roller bottles to an OD600nm= 0.1 in a roller incubator at 37°C. The cells were washed 1x in PBS and resuspended in 50 mL 7H9 OADC glycerol 0.05% tween broth with or without 20mg/L nicotinamide and returned to the incubator. After 7 days, cultures were harvested.
2010-02-24 | GSE18909 | GEO
Project description:Two selected compounds, 2,4-disubstituted pyridine derivatives (11 and 15), revealed significant bactericidal activity against Mycobacterium tuberculosis deposited within human macrophages as well as against biofilm-forming tubercle bacilli. The mass spectrometry-based proteomics (LC-MS/MS) of the wild-type tubercle bacilli growing in the subinhibitory concentration of 11 or 15 revealed 15 overproduced proteins not detectable in the control cells including virulence-related proteins.
2022-11-02 | PXD035807 | Pride
Project description:Rationale: Tuberculosis has a devastating impact on global health by claiming nearly 1.4 million lives each year. During infection Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, produces heterogenous populations some of which don’t produce colonies on agar but grow in liquid media and often require supplementation with culture supernatants or recombinant Resuscitation-promoting factor, thus defined as differentially culturable bacilli. Objectives: to evaluate whether exposure to nitric oxide (NO), a well-known host defence molecule, alters mycobacterial growth phenotypes and drives generation of Rpf-dependent differentially culturable bacilli. Methods: a novel NO donor was synthesised and tested against Mtb and Mycobacterium bovis BCG in vitro, followed by growth assays, flow cytometry analysis and assessment of transcriptomic responses. Resuscitation-promoting factor (Rpf) inhibitors were used to characterise the role of Rpf proteins in the reactivation of NO-treated mycobacteria. Mycobacterial phenotypes were also investigated during infection of THP-1 macrophages activated with retinoic acid and vitamin D3. Measurements and Main Results: differentially culturable mycobacteria were generated after exposure to the novel NO donor or during infection of activated THP-1 cells. Resuscitation of these differentially culturable bacilli was largely abolished by specific Rpf inhibitors. Transcriptomic analysis revealed redox-associated stress signatures mediated by SigH and SigF, with significant down-regulation of ribosome and cell wall architecture genes, including rpfA, rpfB and rpfE, and induction of genes involved in response to thiol stress, sulphur metabolism and iron acquisition. Conclusion: Our study provides mechanistic insights into the generation of Rpf-dependent Mtb during tuberculosis and outlines a critical role of NO in this process.
2023-09-01 | E-MTAB-10776 | biostudies-arrayexpress
Project description:Mycobacterium bovis (M. bovis) and Mycobacterium avium subspecies paratuberculosis (MAP) are important pathogens of cattle, causing bovine tuberculosis and Johne’s disease respectively. M. bovis and MAP infect residential macrophages in the lung and intestines respectively and subvert the macrophage biology to create a survival niche. To investigate this interaction we simultaneously studied the transcriptional response of bovine monocyte-derived macrophages to infection with two strains of M. bovis (AF2122/97 and G18) and two strains of MAP (C & L1).
2017-09-30 | GSE104211 | GEO
Project description:We analyzed the genes expressed, or the transcriptome, of bacilli Mycobacterium bovis BCG Pasteur (wtBCG) and a mutant strain obtained by transposition of the gene BCG_ BCG_2177c (mtBCG), cultured in the presence of a lipid mixture (fatty acids/cholesterol) as main carbon source. Using RNAseq we identified a group of genes that provides novel insight regarding the metabolic pathways and transcriptional regulation, and pathogenic features that were influenced by BCG_2177c gene, a TetR-like repressor, during the lipid metabolism in slow-growing mycobacteria that could be extrapolated to other members of the MTBC.
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Project description:Bovine tuberculosis, caused by Mycobacterium bovis, is a disease of considerable economic importance yet comparatively little is known about the bovine immune response to the disease. Alveolar macrophages are one of the first cells to encounter mycobacteria following infection. In this experiment we investigated the early transcriptional response of bovine alveolar macrophages following infection with M. bovis. The transcriptional response to heat-killed M. bovis was also investigated to look for genes that are only differentially transcribed in response to the live organism.
2010-01-31 | GSE19237 | GEO
Project description:Bovine tuberculosis, caused by Mycobacterium bovis, is a disease of considerable economic importance yet comparatively little is known about the bovine immune response to the disease. Alveolar macrophages are one of the first cells to encounter mycobacteria following infection. In this experiment we investigated the early transcriptional response of bovine alveolar macrophages following infection with M. bovis. The transcriptional response to heat-killed M. bovis was also investigated to look for genes that are only differentially transcribed in response to the live organism. Five-condition experiment, uninfected, live and heat-killed M. bovis-infected bovine alveolar macrophages from five cattle infected for two and four hours. Comparisons were within animal. Dye swaps were incorporated into the design.
2010-01-30 | E-GEOD-19237 | biostudies-arrayexpress
Project description:Mycobacterium bovis is an intracellular pathogen that causes tuberculosis in cattle. Following infection, the pathogen resides and persists inside host macrophages by subverting host immune responses via a diverse range of mechanisms. Here, a high-density bovine microarray platform was used to examine the bovine monocyte-derived macrophage transcriptome response to M. bovis infection relative to infection with the attenuated vaccine strain, M. bovis Bacille CalmetteM-bM-^@M-^SGuM-CM-)rin. Differentially expressed genes were identified (adjusted P-value M-bM-^IM-$ 0.01) and interaction networks generated across an infection time course of 2, 6 and 24 h. The largest number of biological interactions was observed in the 24 h network, which exhibited small-worldscale-free network properties. The 24 h network featured a small number of key hub and bottleneck gene nodes, including IKBKE, MYC, NFKB1 and EGR1 that differentiated the macrophage response to virulent and attenuated M. bovis strains, possibly via the modulation of host cell death mechanisms. These hub and bottleneck genes represent possible targets for immunomodulation of host macrophages by virulent mycobacterial species that enable their survival within a hostile environment. Affymetrix GeneChipM-BM-. Bovine Genome Arrays were used to examine gene expression from a paired comparison of bovine monocyte-derived macrophages (MDM) after in vitro challenge with Mycobacterium bovis versus M. bovis BCG across a time series of 2 hr, 6 hr and 24 hr post-challenge.
2014-08-01 | E-GEOD-59774 | biostudies-arrayexpress
Project description:Macrophages from cattles with different infectious status of bovine tuberculosis have different responses to in vitro Mycobacterium bovis challenge. This is confirmed in our previous study exploring several immune-related genes using qPCR. Microarrays can help us better understand the differences by screening thousands of genes. Monocytes Derived Macrophages from 3 TB-infected cattles and 3 TB-free cattles were challenged with Mycobacterium bovis at a MOI of 10 at 6 hours, and the control group were the same unchallenged macrophages at 6 hours.
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