Transcriptional profile of Mycobacterium tuberculosis in an in vitro model of intraocular tuberculosis
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ABSTRACT:
ORGANISM(S): Mycobacterium tuberculosis Mycobacterium tuberculosis H37Rv
PROVIDER: GSE115292 | GEO | 2018/06/05
REPOSITORIES: GEO
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Project description:Transcriptional profile of Mycobacterium tuberculosis in an in vitro model of intraocular tuberculosis
| PRJNA474483 | ENA
Project description:Intraocular tuberculosis (IOTB) is a significant cause of visual morbidity in TB-endemic countries. However, pathogenesis of Mycobacterium tuberculosis (M. tb) in the ocular compartment is poorly defined. IOTB is paucibacillary in a vast majority of patients although M. tb has been detected in both the retinal pigment epithelial (RPE) cells (Rao et al. 2006) and in the intraocular fluid (IOF) (Aggarwal et al., 2016; Bajgai et al., 2017) in some cases. In this study, we have examined the replication and whole genome transcriptome of M. tb in an IOF model (artificial IOF; AIOF) (Macri et al., 2015). Results show that, as reported for transcriptional profiles of M. tb in sputum (Sharma et al., 2017) and in a starvation model (PBS) (Betts et al., 2002), genes involved in active replication and aerobic respiration are either downregulated or not differentially expressed in the AIOF. In ARPE-19 cells (human RPE cell line), M. tb replicates poorly and exhibits a quiescent phenotype (Abhishek et al., 2018). As in sputum, PBS, and ARPE-19 cells, M. tb in AIOF downregulates genes of the DosR regulon indicating the suppression of dormancy. Importantly, genes encoding ESAT-6 and ESAT-6-like proteins are also downregulated or not differentially expressed in sputum, AIOF and ARPE-19 cells. This is stark contrast to the transcriptome of M. tb in alveolar epithelial cells (Ryndak et al., 2015) and in blood (Ryndak et al. 2014). These results paint a scenario wherein M. tb acquires a replicative and invasive phenotype when it infects a new host and disseminates systemically. However, M. tb acquires a quiescent phenotype upon reaching its final niche in an extrapulmonary site, the ocular environment.
2022-11-30 | GSE216603 | GEO
Project description:Trancriptional Profile of Mycobacterium tuberculosis Replicating at in Artificial Intraocular Fluid
| PRJNA894495 | ENA
Project description:Background: Intraocular tuberculosis (IOTB), an extrapulmonary manifestation of tuberculosis of the eye, has unique and varied clinical presentations with poorly understood pathogenesis. As it is a significant cause of inflammation and visual morbidity, particularly in TB endemic countries, it is essential to study the pathogenesis of IOTB. Clinical and histopathologic studies suggest the presence of Mycobacterium tuberculosis in retinal pigment epithelium (RPE) cells. Methods: A human retinal pigment epithelium (ARPE-19) cell line was infected with a virulent strain of M. tuberculosis (H37Rv). Electron microscopy and colony forming units (CFU) assay were performed to monitor the M. tuberculosis adherence, invasion, and intracellular replication, whereas confocal microscopy was done to study its intracellular fate in the RPE cells. To understand the pathogenesis, the transcriptional profile of M. tuberculosis in ARPE-19 cells was studied by whole genome microarray. Three upregulated M. tuberculosis transcripts were also examined in human IOTB vitreous samples. Results: Scanning electron micrographs of the infected ARPE-19 cells indicated adherence of bacilli, which were further observed to be internalized as monitored by transmission electron microscopy. The CFU assay showed that 22.7 and 8.4% of the initial inoculum of bacilli adhered and invaded the ARPE-19 cells, respectively, with an increase in fold CFU from 1 dpi (0.84) to 5dpi (6.58). The intracellular bacilli were co-localized with lysosomal-associated membrane protein-1 (LAMP-1) and LAMP-2 in ARPE-19 cells. The transcriptome study of intracellular bacilli showed that most of the upregulated transcripts correspond to the genes encoding the proteins involved in the processes such as adherence (e.g., Rv1759c and Rv1026), invasion (e.g., Rv1971 and Rv0169), virulence (e.g., Rv2844 and Rv0775), and intracellular survival (e.g., Rv1884c and Rv2450c) as well as regulators of various metabolic pathways. Two of the upregulated transcripts (Rv1971, Rv1230c) were also present in the vitreous samples of the IOTB patients. Conclusions:M. tuberculosis is phagocytosed by RPE cells and utilizes these cells for intracellular multiplication with the involvement of late endosomal/lysosomal compartments and alters its transcriptional profile plausibly for its intracellular adaptation and survival. The findings of the present study could be important to understanding the molecular pathogenesis of IOTB with a potential role in the development of diagnostics and therapeutics for IOTB.
| S-EPMC6175983 | biostudies-literature
Project description:During lung infection Mycobacterium tuberculosis (Mtb) resides in macrophages and subverts the bactericidal mechanisms of these professional phagocytes. In this work we have analyzed by DNA microarray technique the global transcription profile of Mtb infecting primary human macrophages in order to identify putative bacterial pathogenic factors that can be relevant for the intracellular survival of Mtb. Keywords: time course
2007-12-18 | GSE6209 | GEO
Project description:Studies on human intraocular tuberculosis (IOTB) are extremely challenging. For understanding the pathogenesis of IOTB, it is important to investigate the mycobacterial transcriptional changes in ocular environment. Mice were challenged intravenously with Mycobacterium tuberculosis H37Rv and at 45 days post-infection, experimental IOTB was confirmed based on bacteriological and molecular assays. M. tuberculosis transcriptome was analyzed in the infected eyes using microarray technology. The identified M. tuberculosis signature genes were further validated and investigated in human IOTB samples using real-time polymerase chain reaction. Following intravenous challenge with M. tuberculosis, 45% (5/12) mice showed bacilli in the eyes with positivity for M. tuberculosis ribonucleic acid in 100% (12/12), thus confirming the paucibacillary nature of IOTB similar to human IOTB. M. tuberculosis transcriptome in these infected eyes showed significant upregulation of 12 M. tuberculosis genes and five of these transcripts (Rv0962c, Rv0984, Rv2612c, Rv0974c and Rv0971c) were also identified in human clinically confirmed cases of IOTB. Differentially expressed mycobacterial genes identified in an intravenously challenged paucibacillary mouse IOTB model and presence of these transcripts in human IOTB samples highlight the possible role of these genes for survival of M. tuberculosis in the ocular environment, thus contributing to pathogenesis of IOTB.
| S-EPMC7137459 | biostudies-literature
Project description:In this study, we report the identification of a five-locus copper-inducible regulon in Mycobacterium tuberculosis. The identification of a copper responsive regulon unique to pathogenic Mycobacteria suggests copper homeostasis must be maintained during an infection.
2010-10-27 | GSE23498 | GEO
Project description:Mycobacterium tuberculosis (MTB) is a species of pathogenic bacteria and the causative agent of tuberculosis. The type strain H37Rv has been sequenced in 1998, while many previous studies found its predicted genes exhibit frequent errors, particularly in start codons. Here, we applied a TMPP [(N-Succinimidyloxycarbonylmethyl) tris (2,4,6-trimethoxyphenyl) phosphonium bromide] labeling combined with StageTip separating strategy to characterize the N-terminal peptides. We identified 2,598 annotated proteins, which 1,078 proteins were labeled by TMPP.
2021-06-18 | PXD026846 |
Project description:During lung infection Mycobacterium tuberculosis (Mtb) resides in macrophages and subverts the bactericidal mechanisms of these professional phagocytes. In this work we have analyzed by DNA microarray technique the global transcription profile of Mtb infecting primary human macrophages in order to identify putative bacterial pathogenic factors that can be relevant for the intracellular survival of Mtb. Keywords: time course We compared the global gene expression of the H37Rv strain of Mtb after 4 hours and 24 hours of infection of human macrophage-like THP-1 cells with the gene expression profile of the strain growing exponentially in broth cultures.
2010-05-27 | E-GEOD-6209 | biostudies-arrayexpress
Project description:The human pathogen, Mycobacterium tuberculosis, develops a dormant infection, in which organisms survive within the body. We established a unique in vitro dormancy model based on the characterization of drug-resistance to INH and rifampin. M. tuberculosis cells were maintained in controlled and defined multiple stress conditions with low oxygen (5% dissolved oxygen tension), acid (pH 5.) along with glycerol-deprived medium conditions. To monitor gene expression changes in M. tuberculosis in response to the multiple stresses, we performed microarray analysis at the time point of 1, 2, 3, 6, and 12days after treatment. M. tuberculosis adapting to multiple stresses displayed characteristics associated with persistence in vivo, including entry into a non-replicative state and the repression of genes involved in energy regeneration. Under in vitro multiple-stresses, M. tuberculosis significantly modulated gene expression mainly in response to the starvation stresses. Cells exposed to these multiple stress conditions shows significant drug-resistance. Comparison with other in vivo expression profiles demonstrates induction of several common genes for in vitro dormancy conditions. Keywords: Stress response in time course.
2008-05-01 | GSE10391 | GEO