Project description:Diverse chemical modifications fine-tune the function and metabolism of tRNA. Although tRNA modification is universal in all kingdoms of life, profiles of modifications, their functions, and physiological roles have not been elucidated in most organisms including the human pathogen, Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis. To identify physiologically important modifications, we surveyed the tRNA of Mtb, using tRNA sequencing (tRNA-seq). Reverse transcription-derived error signatures in tRNA-seq predicted the sites and presence of 9 modifications. Several chemical treatments prior to tRNA-seq expanded the number of predictable modifications. Deletion of Mtb genes encoding two modifying enzymes, TruB and MnmA, eliminated their respective tRNA modifications, validating the presence of modified sites in tRNA species.
Project description:We analyzed the genes expressed, or the transcriptome, of bacilli (Mycobacterium tuberculosis) growing in fatty acids as sole carbon source. Using new technologies to massively sequence of RNA molecules we identified a group of genes that provides novel insight regarding the metabolic pathways and transcriptional regulation of latent M. Tuberculosis.
Project description:We sought to identify pathways dysregulated in Mycobacterium tuberculosis upon treatment with the compound C10. We treated M. tuberculosis with DMSO, 5 μM C10, or 25 μM C10 for 48 hours in Sauton's medium and used RNA-sequencing to compare transcriptional profiles.
Project description:To study the entire transcriptional and translational M. tuberculosis response from initial survival to eventual escape from nitric oxide (NO) stress, we exposed exponentially growing M. tuberculosis to 1 mM diethylenetriamine/nitric oxide (DETA/NO) and followed the adaptive response over 48 hours. Samples were obtained from two independent experiments performed in triplicate and we sampled aliquots for transcriptome profiling by RNA sequencing at 20 min, 2 h and 24 h and for mass spectrometry-based shotgun proteomics at 20 min, 40 min, 1 h, 2 h, 4 h, 8 h, 12 h, 24 h and 48 h post NO exposure.
Project description:We sought to identify which genes were dysregulated in hypoxic Mycobacterium tuberculosis upon treatment with C10. We cultured Mycobacterium tuberculosis in an air-tight vessel for 2 weeks in the presence of either DMSO or 50 μM C10, and used RNA-sequencing to compare transcriptional profiles.
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:The aim of this study was to extend our analysis to the obligate human pathogen M. tuberculosis, which has to deal with a more restricted set of environmental variables in terms of nitrogen sources, and to delineate the GlnR regulon, by peforming global analysis of GlnR-DNA interactions by Chromatin Immunoprecipitation and high-throughput sequencing (ChIP-seq) over nitrogen run-out.
Project description:We analyzed the genes expressed, or the transcriptome, of bacilli (Mycobacterium tuberculosis) growing in fatty acids as sole carbon source. Using new technologies to massively sequence of RNA molecules we identified a group of genes that provides novel insight regarding the metabolic pathways and transcriptional regulation of latent M. Tuberculosis. Comparative Transcriptomics between two carbon source (Dextrose, Long Fatty Acids), at two states of growth (Exponential and Stationary Phase)
Project description:The ability of Mycobacterium tuberculosis (Mtb) to adopt heterogeneous physiological states, underlies it’s success in evading the immune system and tolerating antibiotic killing. Drug tolerant phenotypes are a major reason why the tuberculosis (TB) mortality rate is so high, with over 1.8 million deaths annually. To develop new TB therapeutics that better treat the infection (faster and more completely), a systems-level approach is needed to reveal the complexity of network-based adaptations of Mtb. Here, we report the transcriptional response of Mtb to the drug isoniazid. We performed transcriptomic sequencing (RNA-seq) on Mtb bacilli at 4, 24, 72 h following exposure to the drug.
Project description:The ability of Mycobacterium tuberculosis (Mtb) to adopt heterogeneous physiological states, underlies it’s success in evading the immune system and tolerating antibiotic killing. Drug tolerant phenotypes are a major reason why the tuberculosis (TB) mortality rate is so high, with over 1.8 million deaths annually. To develop new TB therapeutics that better treat the infection (faster and more completely), a systems-level approach is needed to reveal the complexity of network-based adaptations of Mtb. Here, we report the transcriptional response of Mtb to the drug Moxifloxacin. We performed transcriptomic sequencing (RNA-seq) on Mtb bacilli at 4, 24, 72 h following exposure to the drug.