Project description:Transcriptional profiling of mycobacterium tuberculosis clinical isolates in China comparing extensively drug-resistant tuberculosis with drug sensitive one.
Project description:Transcriptional profiling of mycobacterium tuberculosis clinical isolates in China comparing extensively drug-resistant tuberculosis with drug sensitive one. The same condition experiment. The samples were from the different drug-resistant strains. Only one replicate.
Project description:In Mycobacterium tuberculosis, the PhoPR two-component regulatory system controls production and secretion of proteins and lipid virulence effectors. Several mutations, present in phoR of Mycobacterium canettii relative to M. tuberculosis, impact the expression of the PhoP regulon and the pathogenicity of the strains. Here, we analyse by RNA-seq the expression profile of PhoP-regulated genes between the two M. tuberculosis strains H37Rv and HN878 and the two M. canettii isolates STB-Ks and STB-Kr.
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.
Project description:Mycobacterium tuberculosis has the ability to persist within the host in a clinically latent stage. One important condition believed to contribute to latency is reduced access to oxygen but the response of M. tuberculosis to hypoxia is partially characterized. Virtually all dormant models against tuberculosis the vaccine tested in animals used laboratory strains H37Rv or Erdman strains. But major outbreaks of TB occur with the strains that have widely different genotypes and phenotypes compare to H37Rv. In this study, we used a commercial oligonucleotide microarray to determine the overall transcriptional response of lab strain (H37Rv) and most prevalent strains of Mycobacterium tuberculosis from South India S7 and S10 to hypoxia. Analysis of microarray results revealed that a total of 1161 genes are differentially regulated in H37Rv, among them 659 genes are upregulated and 502 genes are down regulated when > 1.5 fold change was taken as cut off. Microarray data of clinical isolates showed total of 790 genes are differentially regulated in S7 clinical isolates among which 453 are upregulated and 337 are down regulated. Interestingly numerous genes are differentially regulated in S10 clinical isolates (total of 2805 genes) and 1463 are upregulated and 1342 genes are down regulated during reduced oxygen model (Wayne’s model). Real-time quantitative RT-PCR was performed for few genes to validate the microarray results. To our knowledge, this genome-wide transcriptomics approach has produced the first insights into the response of South Indian prevalent clinical strains of M. tuberculosis when exposed to reduced oxygen stress.
