Project description:The ability of Mycobacterium tuberculosis (Mtb) to tolerate antibiotics is a major impediment in the treatment of tuberculosis. This antibiotic tolerance is influenced by the host cells in which the bacteria reside, as Mtb senses host cues, and the bacterial response can provide an enhanced ability to withstand anti-TB drugs. Previouslyt, we have shown that Mtb exhibits redox heterogeneity in terms of its mycothiol redox potential (EMSH) giving rise to three broad subpopulations EMSH-reduced, EMSH-basal, and EMSH-oxidized Mtb specifically inside the macrophages. Among these, the EMSH-reduced Mtb exhibit enahnced tolerance to several anti-TB drugs while the EMSH-basal and EMSH-oxidized subpopulations are more susceptible. In this study, we explored the transcriptomic level differences between macrophages that harbor the antibiotic tolerant Mtb and those harboring antibiotic susceptible Mtb to get a mechanistic understanding of host factors that influence drug tolerance in intracellular Mtb.
Project description:The ability of Mycobacterium tuberculosis (Mtb) to tolerate antibiotics is a major impediment in the treatment of tuberculosis. This antibiotic tolerance is influenced by the host cells in which the bacteria reside, as Mtb senses host cues, and the bacterial response can provide an enhanced ability to withstand anti-TB drugs. Previouslyt, we have shown that Mtb exhibits redox heterogeneity in terms of its mycothiol redox potential (EMSH) giving rise to three broad subpopulations EMSH-reduced, EMSH-basal, and EMSH-oxidized Mtb specifically inside the macrophages. Among these, the EMSH-reduced Mtb exhibit enahnced tolerance to several anti-TB drugs while the EMSH-basal and EMSH-oxidized subpopulations are more susceptible. In this study, we have discovered a novel host-directed therapy molecule- meclizine, which enhances the drug susceptible population and diminishes the tolerant population.
Project description:THP-1 Macrophages were infected with Mycobacterium tuberculosis clinical isolates from Xinjiang, China, and H37Rv for 24 hours, respectively, and their transcriptomes were sequenced to investigate the specific biological processes that occur after infection of macrophages with Mycobacterium tuberculosis clinical isolates from Xinjiang, China.
Project description:Pulse chase SILAC was used to identify protein turnover within human macrophages infected with mycobacterium tuberculosis CDC1551, a ppe38-71 mutant strain, a complemented strain and an uninfected control.
Project description:Transcriptional profiling of Mycobacterium tuberculosis mRNA enriched from host-pathogen samples from in vivo alveolar macrophages (Mus musculus).
Project description:Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, a chronic granulomatous disease. Mtb is mostly restricted to humans and seldom causes disease in animals. M. bovis (Mbv) on the other hand causes tuberculosis in cows (bovine tuberculosis) and several wild animals. Each of these pathogens therefore has unique host adaptations and the host- and pathogen-specific factors driving this differential tropism still remain largely unknown. Here we profiled the secretomes of Mtb- and Mbv-infected bovine macrophages to characterise host-specific responses to each pathogen.