Mycobacterium tuberculosis hijacks host primary transcripts
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA393396 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Intracellular pathogens requires efficient mechanism adapting the environment inside of host cells. Here we show that the transcriptomes of the cellular mycobacterium tuberculosis and of those released from the infected macrophage cells contain a large fraction of human transcripts by RNA polymerase II. Uptake of host pre-mRNAs is coincident with the co-localization of M. tuberculosis with nuclear membrane. The infective M. tuberculosis selectively uptakes snoRNAs.The intracellular pathogens has a preferable capability in taking pre-mRNAs. The host transcripts are not generally spliced nor translated.We suggest that the intracellular bacterium has acquired a mechanism to take transcripts from the host cell nuclus as its own nutrient supply and may help them to survive with hosts.
2021-10-23 | GSE100897 | GEO
Project description:RNA-Seq results accompanying submission of a manuscript: "Depletion of CCA-adding enzyme in Mycobacterium tuberculosis leads to polyadenylation of transcripts and precursor tRNAs" describing the function of the Rv3907c gene product as a CCA-adding enzyme in Mycobacterium tuberculosis.
2023-09-30 | GSE220711 | GEO
Project description:Pyrazinamide (PZA) is one of the first line antibiotics used for the treatment of tuberculosis (TB). we have used human monocyte and a mouse model of pulmonary TB to investigate whether treatment with PZA, in addition to its known anti-mycobacterial properties, modulate the host immune response during Mycobacterium tuberculosis (Mtb) infection.
2013-06-28 | GSE48027 | GEO
Project description:Macrophages play an essential role in the early immune response to Mycobacterium tuberculosis and are the cell type preferentially infected in vivo. Primary macrophages and macrophage-like cell lines are commonly used as infection models, although the physiological relevance of cell lines, particularly for host-pathogen interaction studies, is debatable. Here we use high-throughput RNA-sequencing to analyse transcriptome dynamics of two macrophage models in response to M. tuberculosis infection. Specifically, we study the early response of bone marrow-derived mouse macrophages and cell line J774 to infection with live and -irradiated (killed) M. tuberculosis. We show that infection with live bacilli specifically alters the expression of host genes such as RSAD2, IFIT1/2/3 and RIG-I, whose potential roles in resistance to M. tuberculosis infection have not yet been investigated. In addition, the response of primary macrophages is faster and more intense than that of J774 cells in terms of number of differentially expressed genes and magnitude of induction/repression. Our results point to potentially novel processes leading to immune containment early during M. tuberculosis infection, and support the idea that important differences exist between primary macrophages and cell lines, which should be taken into account when choosing a macrophage model to study host-pathogen interactions.
2016-10-18 | GSE88801 | GEO
Project description:The success of Mycobacterium tuberculosis (Mtb) as pathogen is tightly linked to its ability to recalibrate host metabolic processes in infected host macrophages. Correspondingly, analysis of RNA-sequencing datasets showed altered gene expression of key metabolic enzymes involved in NAD+, creatine, glucose and glutamine metabolism (e.g NAMPT, IDO1, SLC6A8, CKB, HK2) in Mtb-infected M2 macrophages.
2020-04-16 | GSE148731 | GEO
Project description:Pyrazinamide (PZA) is one of the first line antibiotics used for the treatment of tuberculosis (TB). we have used human monocyte and a mouse model of pulmonary TB to investigate whether treatment with PZA, in addition to its known anti-mycobacterial properties, modulate the host immune response during Mycobacterium tuberculosis (Mtb) infection. Mice were infected with Mtb and treatment with PZA was started at 28 days post-infection. At 42 days and 63 days post-infection, group of animals were euthanized and lung tissue was collected to isolate total RNA and used in microarray experiments. Mtb-infected, untreated animals served as controls.
2013-06-28 | E-GEOD-48027 | biostudies-arrayexpress
Project description:Metformin, the most widely administered diabetes drug, has been proposed as a candidate for host directed therapy for tuberculosis although very little is known about its effects on human host responses to Mycobacterium tuberculosis. When added in vitro to PBMCs isolated from healthy non-diabetic volunteers, metformin increased glycolysis, inhibited the mTOR targets, strongly reduced M. tuberculosis induced production of TNF-alpha (-58%), IFN-gamma (-47%) and IL-beta (-20%), while increasing phagocytosis. In healthy subjects, in vivo metformin intake induced significant transcriptional changes in whole blood and isolated PBMCs, with substantial down-regulation of genes related to inflammation and the type 1 interferon response. Metformin intake also increased monocyte phagocytosis (by 1.5 to 2 fold) and ROS production (+20%). These results show that metformin in humans has a range of potentially beneficial effects on cellular metabolism, immune function and gene-transcriptional level, that affect innate host responses to M. tuberculosis. This underlines the importance of cellular metabolism for host immunity and supports a role for metformin as host-directed therapy for tuberculosis.
2019-06-16 | GSE102677 | GEO
Project description:Metformin, the most widely administered diabetes drug, has been proposed as a candidate for host directed therapy for tuberculosis although very little is known about its effects on human host responses to Mycobacterium tuberculosis. When added in vitro to PBMCs isolated from healthy non-diabetic volunteers, metformin increased glycolysis, inhibited the mTOR targets, strongly reduced M. tuberculosis induced production of TNF-α (-58%), IFN-gamma (-47%) and IL-1β (-20%), while increasing phagocytosis. In healthy subjects, in vivo metformin intake induced significant transcriptional changes in whole blood and isolated PBMCs, with substantial down-regulation of genes related to inflammation and the type 1 interferon response. Metformin intake also increased monocyte phagocytosis (by 1.5 to 2 fold) and ROS production (+20%). These results show that metformin in humans has a range of potentially beneficial effects on cellular metabolism, immune function and gene-transcriptional level, that affect innate host responses to M. tuberculosis. This underlines the importance of cellular metabolism for host immunity and supports a role for metformin as host-directed therapy for tuberculosis.
2019-06-16 | GSE102633 | GEO
Project description:The global burden of tuberculosis (TB) is aggravated by the continuously increasing emergence of drug resistance, highlighting the need for innovative therapeutic options. The concept of host-directed therapy (HDT) as adjunctive to classical antibacterial therapy with antibiotics represents a novel and promising approach for treating TB. Here, we have focused on repurposing the clinically used anticancer drug tamoxifen, which was identified as a molecule with strong host-directed activity against intracellular Mycobacterium tuberculosis (Mtb). Using a primary human macrophage Mtb infection model, we demonstrate the potential of tamoxifen against drug-sensitive as well as drug-resistant Mtb bacteria. The therapeutic effect of tamoxifen was confirmed in an in vivo TB model based on Mycobacterium marinum infection of zebrafish larvae. Tamoxifen had no direct antimicrobial effects at the concentrations used, confirming that tamoxifen acted as an HDT drug. Furthermore, we demonstrate that the antimycobacterial effect of tamoxifen is independent of its well-known target the estrogen receptor (ER) pathway, but instead acts by modulating autophagy, in particular the lysosomal pathway. Through RNA sequencing and microscopic colocalization studies, we show that tamoxifen stimulates lysosomal activation and increases the localization of mycobacteria in lysosomes both in vitro and in vivo, while inhibition of lysosomal activity during tamoxifen treatment partly restores mycobacterial survival. Thus, our work highlights the HDT potential of tamoxifen and proposes it as a repurposed molecule for the treatment of TB.
2022-11-29 | GSE178919 | GEO
Project description:Analysis of Metfromin induced changes in the lung cells of Mycobacterium tuberculosis infected mouse at gene expression level. The hypothesis tested in the present study was whether metformin has any effect on the host immune response in Mycobacterium tuberculosis infected mice? Results provide important information on the effect of metformin on the inflammatory response and immune activation associated with mycobacterial infection. In conclusion, Metfromin normalizes the chronic inflammation associated with Mycobacterium tuberculosis infection.
2014-12-02 | GSE57275 | GEO