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:<p>Gene rv3722c of Mycobacterium tuberculosis is essential for in vitro growth, and encodes a putative pyridoxal phosphate-binding protein of unknown function. Here we use metabolomic, genetic and structural approaches to show that Rv3722c is the primary aspartate aminotransferase of M. tuberculosis, and mediates an essential but underrecognized role in metabolism: nitrogen distribution. Rv3722c deficiency leads to virulence attenuation in macrophages and mice. Our results identify aspartate biosynthesis and nitrogen distribution as potential species-selective drug targets in M. tuberculosis.</p>
Project description:Identification of genetic polymorphisms associated with inter-individual variation in immune response to Mycobacterium tuberculosis infection.
Project description:Identification of genetic polymorphisms associated with inter-individual variation in immune response to Mycobacterium tuberculosis infection.
Project description:In other bacteria, arginine induces the expression of genes involved in arginine catabolism. This study obtained the identification of genes involved in the arginine metabolism of Mycobacterium tuberculosis. Mycobacterium tuberculosis was cultured with arginine or ammonium chloride as sole nitrogen source. In the log phase of growth, RNA was isolated and whole genome expression was determined. The study contains three biological replicates.
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:The stringent response, involving the regulatory molecules inorganic polyphosphate (poly P) and (p)ppGpp, is believed to mediate Mycobacterium tuberculosis persistence. In this study, we identified a novel exopolyphosphatase responsible for poly P hydrolysis. Using two different poly P-accumulating M. tuberculosis recombinant strains, we found that increased poly P content drives the organisms into early growth arrest, and contributes to tolerance to the cell wall-active agent isoniazid, increased resistance to stress conditions, and improved survival in macrophages. Transcriptomic and metabolomics analysis revealed metabolic downshift manifested by reduced expression of the transcriptional and translational machinery, and shift from utilization of glucose as a carbon source. In summary, regulation of the poly P balance is critical for persister formation in M. tuberculosis. The transcriptome of poly P accumulation strains, Rv1026 knock-down and ppk1 knock-in were compared to empty vector strains by RNA-seq.
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:Mycobacterium tuberculosis (Mtb) persists within macrophages, yet how different host species shape bacterial state remains poorly understood. Here, we directly compared the intracellular transcriptome of Mtb during infection of human and mouse macrophages, revealing distinct host-imposed microenvironments that drive the pathogen into separable metabolic states. Lipid metabolism and regulatory circuits were prominently remodeled, with mouse macrophages inducing iron- and oxidative-stress responses while human macrophages promoted fatty acid import programs.