title: Deciphering the metabolic response of Mycobacterium tuberculosis to nitrogen stress.
abstract: A key component to the success of Mycobacterium tuberculosis as a pathogen is the ability to sense and adapt metabolically to the diverse range of conditions encountered in vivo, such as oxygen tension, environmental pH and nutrient availability. Although nitrogen is an essential nutrient for every organism, little is known about the genes and pathways responsible for nitrogen assimilation in M. tuberculosis. In this study we have used transcriptomics and chromatin immunoprecipitation and high-throughput sequencing to address this. In response to nitrogen starvation, a total of 185 genes were significantly differentially expressed (96 up-regulated and 89 down regulated; 5% genome) highlighting several significant areas of metabolic change during nitrogen limitation such as nitrate/nitrite metabolism, aspartate metabolism and changes in cell wall biosynthesis. We identify GlnR as a regulator involved in the nitrogen response, controlling the expression of at least 33 genes in response to nitrogen limitation. We identify a consensus GlnR binding site and relate its location to known transcriptional start sites. We also show that the GlnR response regulator plays a very different role in M. tuberculosis to that in non-pathogenic mycobacteria, controlling genes involved in nitric oxide detoxification and intracellular survival instead of genes involved in nitrogen scavenging.
authors.affiliation: MRC Centre for Molecular Bacteriology and Infection, Department of Medicine, Imperial College London, London, SW7 2AZ, UK.
authors.forename: Kerstin J
authors.initials: KJ
authors.lastname: Williams
authors.affiliation: MRC Centre for Molecular Bacteriology and Infection, Department of Medicine, Imperial College London, London, SW7 2AZ, UK.
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Jenkins
authors.affiliation: Centre for Integrative Systems Biology and Bioinformatics, Imperial College London, London, SW7 2AZ, UK.
authors.forename: Geraint R
authors.initials: GR
authors.lastname: Barton
authors.affiliation: Centre for Integrative Systems Biology and Bioinformatics, Imperial College London, London, SW7 2AZ, UK.
authors.forename: William A
authors.initials: WA
authors.lastname: Bryant
authors.affiliation: MRC Centre for Molecular Bacteriology and Infection, Department of Medicine, Imperial College London, London, SW7 2AZ, UK.
authors.forename: Nitya
authors.initials: N
authors.lastname: Krishnan
authors.affiliation: MRC Centre for Molecular Bacteriology and Infection, Department of Medicine, Imperial College London, London, SW7 2AZ, UK.|Centre for Integrative Systems Biology and Bioinformatics, Imperial College London, London, SW7 2AZ, UK.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Robertson
mesh_terms: D064751:Ammonium Compounds / Q000378:metabolism; D001224:Aspartic Acid / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism*; D001665:Binding Sites; D002473:Cell Wall / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D053858:Metabolic Networks and Pathways; D009169:Mycobacterium tuberculosis / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D009584:Nitrogen / Q000378:metabolism*; D011485:Protein Binding; D020218:Response Elements; D013312:Stress, Physiological
chemical_list: D064751:Ammonium Compounds; D001426:Bacterial Proteins; D001224:Aspartic Acid; D009584:Nitrogen