Project description:Tuberculosis (TB) remains a deadly disease. The genetic diversity of Mycobacterium tuberculosis was neglected in the past, but is increasingly recognized as a determinant of immune responses and clinical outcomes of TB. However, how this bacterial diversity orchestrates immune responses to direct differences in TB severity remains unknown. We studied 681 patients with pulmonary TB and found that phylogenetically related M. tuberculosis isolates from cases with mild disease induced robust cytokine responses in macrophages. In contrast, isolates associated with severe TB cases failed to do so. Using representative isolates, we show that M. tuberculosis inducing a low cytokine response in macrophages also diminished activation of cytosolic surveillance systems, including cGAS and the inflammasome, suggesting a novel mechanism of immune escape. Isolates exhibiting this evasion strategy carried mutations in various components of the ESX-I secretion system. We conclude that host interactions with different M. tuberculosis strains results in variable TB severity.
2020-02-26 | GSE138580 | GEO
Project description:Molecular Epidemiology of Mycobacterium tuberculosis complex (MTBC) in Ghana
Project description:This study uses microarray analyses to examine baseline gene expression profiles for Mycobacterium tuberculosis complex clinical isolates relative to reference strain CDC1551 during log phase growth in vitro in 7H9 broth. For this in vitro analyses, log-phase mycobacteria in starter cultures grown to mid-log from frozen stocks were inoculated into 7H9-OADC medium in 25-cm2 vented flasks at an OD of ~0.05 and grown without shaking for ~1 week to an OD of ~0.5-0.6.
Project description:Transcriptional profiling of mycobacterium tuberculosis clinical isolates in China comparing extensively drug-resistant tuberculosis with drug sensitive one.
Project description:This study uses microarray analyses to examine baseline gene expression profiles for Mycobacterium tuberculosis complex clinical isolates relative to reference strain CDC1551 during log phase growth in vitro in 7H9 broth. For this in vitro analyses, log-phase mycobacteria in starter cultures grown to mid-log from frozen stocks were inoculated into 7H9-OADC medium in 25-cm2 vented flasks at an OD of ~0.05 and grown without shaking for ~1 week to an OD of ~0.5-0.6. Computed
Project description:The global diversity of Mycobacterium tuberculosis comprises at least seven lineages, each with its distinct geographic distribution. The aim of this experiment was to perform a comparative analysis of two of these lineages: Lineage 1 and Lineage 2. The former is found around the rim of the Indian ocean and in south-east Asia, while the latter is widely spread throughout Asia and shows an increasing global spread. We have chosen three fully drug susceptible clincal isolates to represent each of the two lineages. We performed RNAseq analysis on rRNA depleted samples isolated from cultures during mid-log phase. Each strain was measured in triplicate.
Project description:Tuberculosis (TB), caused by Mycobacterium tuberculosis complex (MTBC) pathogens, remains a global health threat. While bacterial genetic adaptations during host adaptation are poorly understood, phase variation in genomic homopolymeric tracts (HT) may drive pathogenicity evolution. Here, we demonstrate that M. bovis exploits HT insertion mutations in the fumarate reductase-encoding frd operon to subvert host immunometabolism. This study investigates the immunometabolic consequences of frd operon mutations in M. bovis-infected macrophages. RNA sequencing (RNA-seq) was performed on mouse bone marrow-derived macrophages (BMDMs) infected with wild-type M. bovis or its isogenic Δfrd mutant for 12 hours. Comparative transcriptomic analysis identified 192 upregulated and 344 downregulated genes in Δfrd-infected BMDMs, revealing significant suppression of innate immune pathways (e.g., defense response to Gram-positive bacteria, hypoxia adaptation) and upregulation of neutrophil chemotaxis/IL-17 signaling. Notably, Δfrd infection downregulated Gapdh (a glycolytic gatekeeper) and disrupted glucose metabolism-related pathways.