Project description:Transcriptional profiling of mycobacterium tuberculosis clinical isolates in China comparing extensively drug-resistant tuberculosis with drug sensitive one.
Project description:Monocytes play a critical role during infection with Mycobacterium tuberculosis (Mtb). They are recruited to the lung where they participate in the contention of infection. Alternatively, inflammatory monocytes may help in prolonging inflammation or serve as niches for Mtb infection. Also, monocyte response to infection may vary depending on the particularities of the clinical isolate of Mtb from which they are infected. In this pilot study, using microarrays we have examined the global mRNA profiles of circulating human monocytes from healthy individuals and patients with active tuberculosis (TB).
Project description:Phagosome acidification is one of the challenges faced by Mycobacterium tuberculosis during infection. This intracellular pathogen is known to adapt to its stressful environment though stress response pathways and by secreting proteins to modify the host immune response for survival and proliferation. However, M. tuberculosis also holds the potential to form viable but non-replicating (VBNR) and antibiotic tolerant persisters in response to environmental stress, including acid stress. In this study we used a in vitro acid stress model to stimulate the formation of a VBNR subpopulation in a M. tuberculosis clinical isolate with an increased propensity to form VBNR bacteria. Mass spectrometry-based proteomics was used to characterize the cellular proteome and culture filtrate proteome of actively replicating (pH 6,5) and VBNR enriched (pH 4,5) cultures. We show that in response to acid stress, M. tuberculosis S169 increases the expression of known stress response proteins, including the methyltransferase Rv1405c and the acid stress response two-component regulatory protein TcrX. Interestingly, we found that the dormancy response regulon components were less abundant in acid stressed M. tuberculosis S169. Our protein aggregation capture culture filtrate proteomic approach revealed that the culture filtrates of low pH stressed M. tuberculosis S169 contained less proteins than that of actively replicating cultures. We identified several proteins previously implicated in M. tuberculosis persistence, including toxin-antitoxin proteins (VapC51 and VapB10), the chorismate mutase (Rv1885c), and several uncharacterized proteins. The observed differences identified in the characterisation of this clinical isolate in comparison to published M. tuberculosis H37Rv highlights the need to investigate M. tuberculosis clinical isolates for a more representative understanding of the tuberculosis stress response.
Project description:Phagosome acidification is one of the challenges faced by Mycobacterium tuberculosis during infection. This intracellular pathogen is known to adapt to its stressful environment though stress response pathways and by secreting proteins to modify the host immune response for survival and proliferation. However, M. tuberculosis also holds the potential to form viable but non-replicating (VBNR) and antibiotic tolerant persisters in response to environmental stress, including acid stress. In this study we used a in vitro acid stress model to stimulate the formation of a VBNR subpopulation in a M. tuberculosis clinical isolate with an increased propensity to form VBNR bacteria. Mass spectrometry-based proteomics was used to characterize the cellular proteome and culture filtrate proteome of actively replicating (pH 6,5) and VBNR enriched (pH 4,5) cultures. We show that in response to acid stress, M. tuberculosis S169 increases the expression of known stress response proteins, including the methyltransferase Rv1405c and the acid stress response two-component regulatory protein TcrX. Interestingly, we found that the dormancy response regulon components were less abundant in acid stressed M. tuberculosis S169. Our protein aggregation capture culture filtrate proteomic approach revealed that the culture filtrates of low pH stressed M. tuberculosis S169 contained less proteins than that of actively replicating cultures. We identified several proteins previously implicated in M. tuberculosis persistence, including toxin-antitoxin proteins (VapC51 and VapB10), the chorismate mutase (Rv1885c), and several uncharacterized proteins. The observed differences identified in the characterisation of this clinical isolate in comparison to published M. tuberculosis H37Rv highlights the need to investigate M. tuberculosis clinical isolates for a more representative understanding of the tuberculosis stress response.
Project description:Comparison of gene expression profile of the whiB4 mutant strain of Mycobacterium tuberculosis with the wild type Mycobacterium tuberculosis H37RV Mtb WhiB4 mutant mRNA was compared with the mRNA of wtMtb H37RV under aerobic conditons
Project description:This SuperSeries is composed of the following subset Series: GSE36341: mRNA degradation in Mycobacterium tuberculosis under aerobic conditions GSE36342: mRNA degradation in Mycobacterium smegmatis under aerobic conditions GSE36343: mRNA degradation in Mycobacterium tuberculosis during cold and hypoxic stress GSE36344: mRNA degradation in Mycobacterium tuberculosis with DosR ectopically induced Refer to individual Series