Mycobacterium tuberculosis gene expression in response to thioridazine (THZ)
Ontology highlight
ABSTRACT:
ORGANISM(S): Mycobacterium tuberculosis
SUBMITTER: Noton Dutta
PROVIDER: E-GEOD-16626 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Oxadiazolone (OX) derivatives have been investigated for their antimycobacterial activity against three pathogenic slow-growing mycobacteria: Mycobacterium marinum, Mycobacterium bovis BCG and the avirulent Mycobacterium tuberculosis (M. tb) mc26230. The encouraging MIC values obtained prompted us to test them against virulent M. tb H37Rv growth either in broth medium or inside macrophages. The OX compounds displayed a diversity of action and were found to act either on extracellular M. tb growth only with moderated MIC, or both intracellularly on infected macrophages as well as extracellularly on bacterial growth. One OX derivatives, HPOX, was selected and used in a competitive labelling/enrichment assay against the activity-based probe Desthiobiotin-FP in order to identify its putative target(s). This approach, combined with mass spectrometry, identified 18 potential candidates, all being serine or cysteine enzymes involved in M. tb lipid metabolism and/or in cell wall biosynthesis. Among them, Ag85A, CaeA, TesA, KasA and MetA have been reported as essential for in vitro growth of M. tb and/or its survival and persistence inside macrophages. Overall, our findings support the assumption that OX derivatives may represent a novel class of multi-target inhibitors leading to the arrest of M. tb growth through a cumulative inhibition of a large number of Ser- and Cys-containing enzymes involved in various important physiological processes.
2018-09-25 | PXD010255 | Pride
Project description:Mtb appears to have developed specialized biomolecular infrastructure to survive and persist within granulomas, where it is subjected to a diverse set of stress conditions. One of these stress conditions is hypoxia. We hypothesized that host cell response is radically altered with hypoxia stressed Mtb and designed in-vitro experiments to study this phenomenon. Hypoxia-stressed as well as aerobically grown Mtb were used to infect rhesus macaque bone marrow derived macrophages (Rh-BMDMs) and the host global transcriptional response compared. Using 4 x44 k Agilent arrays specific for rhesus macaque genome, we tested in biological duplicate the effect of aerogically grown Mtb on rhesus macaque BMDMs and compared this to the corresponding effect of the hypoxia-conditioned Mtb on rhesus macaque BMDMs
2013-05-22 | E-GEOD-47163 | biostudies-arrayexpress
Project description:2 experiments: (1) Mtb, Tween vs Cholesterol at 3 & 24hrs (2) CDC1551 vs kstR mutant of CDC1551, with and w/o Cholesterol In triplicate, dye flips included.
2010-06-20 | E-GEOD-13978 | biostudies-arrayexpress
Project description:Background: Conflicting results have been reported about the role of the two-component sensor and transcriptional regulator DosS/DosR, controlling the expression of the dormancy DosR regulon, for in vivo virulence of M. tuberculosis. Here, we have used a new approach to further analyze the relevance of the dosRS system, by driving DosR (Rv3133c) expression under the control of a constitutive promoter (phsp60). Methodology/Principal Findings: M. tuberculosis H37Rv constitutively expressing the transcriptional regulator DosR (Mtb::DosR) was compared to wild type M. tuberculosis (Mtb+/+) for in vitro growth kinetics and expression of the target genes of the DosR dormancy regulon, for in vivo virulence and for immunogenicity in mice. Under aerobic conditions, hsp60-driven DosR induced the expression of 28 out of 39 tested DosR regulon genes. In vitro growth characteristics were comparable for both strains, but Mtb::DosR showed an attenuated in vivo phenotype in immunocompetent mice, as indicated by reduced bacterial replication, reduced pulmonary immunopathology, reduced cachexia and significantly prolonged survival time as compared Mtb+/+. In immunodeficient SCID mice, Mtb::DosR was fully virulent. RT-qPCR analysis revealed a strong and comparable pulmonary TNF-?? and IL-23 expression following intratracheal infection, whereas IL-12 and IL-17 expression was slightly higher with wild type Mtb+/+. Finally, mice persistently infected with Mtb::DosR for 8 months showed five to tenfold higher lung IFN-?? responses against ten of the 48 DosR regulon encoded antigens (Rv1733c, Rv1734, Rv1738, Rv1996, Rv1997, Rv2029c, Rv2623, Rv2627c, Rv2628 and Rv3127) than mice actively infected with Mtb+/+. In spleen however, DosR regulon encoded antigen specific IFN-?? responses were similar in both groups. Conclusions/Significance. Collectively, these results suggest that increased DosR regulon encoded antigen specific pulmonary T cell responses are responsible for the attenuated phenotype of Mtb::DosR and that infection with Mtb::DosR could be used as a new animal model for studying key aspects of latent tuberculosis. Set of arrays that are part of repeated experiments
2012-06-12 | E-GEOD-19838 | biostudies-arrayexpress
Project description:Following phagocytosis by macrophages, Mycobacterium tuberculosis (Mtb) senses the intracellular environment and remodels its gene expression for growth in the phagosome. Abramovitch et.al. in this current study identified an Acid and Phagosome Regulated (aprABC) locus that is unique to the Mtb complex and whose gene expression is induced during growth in acidic environments in vitro and in macrophages. The authors propose a model where phoP senses the acidic pH of the phagosome and induces aprABC expression to fine-tune processes unique for intracellular adaptation of Mtb complex bacteria. This study uses microarray analyses to compare transcriptional responses of wild type Mycobacterium tuberculosis (CDC1551) to aprABC locus deletion mutants and the phoP transposon mutant. The bacteria were grown to early log phase in vented T-75 standing flasks containing 12 mL of pH 7.0 7H9 OADC medium. Transcript levels of the wild type bacteria were compared to the following mutants: aprABC null, aprBC null, aprC null, phoP::Tn mutant.
2011-07-09 | E-GEOD-22854 | biostudies-arrayexpress
Project description:Infants are vulnerable to disseminated forms of tuberculosis and suffer disproportionately high morbidity and mortality, but the reasons for this are unknown. We hypothesized that since alveolar macrophages (AMs) are critical in the uptake and containment of Mycobacterium tuberculosis (Mtb) in the lung, their function may be impaired in early life. We developed a method of obtaining AMs during rigid bronchoscopy of healthy infants with suspected airway abnormality. RNAseq analysis of Mtb-stimulated AMs from 4 infants and 4 adults was performed.
2020-03-12 | E-MTAB-7679 | biostudies-arrayexpress
Project description:Using cell-based approaches and experimental mouse models for pulmonary TB we unveiled MDSCs as new myeloid populations directly interacting with Mycobacterium tuberculosis (Mtb). MDSCs readily phagocytosed Mtb, released proinflammatory (IL-6, IL-1M-NM-1) and immunomodulatory (IL-10) cytokines while retaining their suppressive capacity. MDSCs were identified at the site of infection in disease-resistant and -susceptible mice during pulmonary TB. Excessive MDSC accumulation in lungs correlated with elevated surface expression of IL-4RM-NM-1 and heightened TB lethality. Microarray experiments were performed as dual-color hybridizations on Agilent mouse whole genome catalog 44K arrays. To compensate for dye-specific effects, a dye-reversal color-swap was applied.
2014-12-21 | E-GEOD-57124 | biostudies-arrayexpress
Project description:The gene expression profiles of Mtb after treatment at the minimal inhibitory concentration (MIC) or 4 X MIC at an early stage (up to 6 hours) was compared to untreated Mtb.
2009-07-08 | GSE16626 | GEO
Project description:Bacteria commonly adapt to stresses by altering gene expression. To understand the response of M. tuberculosis (MTB) to various antibacterial agents, we performed transcriptomics on MTB bacilli exposed to several test compounds as well as known drugs (capreomycin, cycloserine, ethionamide, isoniazid, kanamycin, moxifloxacin, PA-824, rifampicin, streptomycin). Bacteria were exposed for 16 hrs to various concentrations of each drug (different multiples of the compound's MIC), as noted in the title of each sample. RNA was isolated and applied to arrays provided by TIGR under the NIAID contract N01-AI-15447
2015-11-11 | E-GEOD-71200 | biostudies-arrayexpress
Project description:The numerous sigma factors present in Mycobacterium tuberculosis (MTB) are indicative of adaptability to different environmental conditions. In this report we describe the sigma factor B (sigB) regulon and the phenotypes of a MTB sigB mutant strain exposed to different stresses like SDS and Diamide. This experiment set compares expression profiles between H37Rv wild type and H37Rv sigB null mutant as well as under different stress conditions. Both H37Rv wild type and H37Rv sigB null mutants were treated with either 0.05% SDS or 5mM Diamide for 60 min and their expression profiles were compared with untreated wild type or mutant controls. Biological Replicate
2010-06-25 | E-GEOD-15976 | biostudies-arrayexpress