title: The pleiotropic transcriptional response of Mycobacterium tuberculosis to vitamin C is robust and overlaps with the bacterial response to multiple intracellular stresses.
abstract: Mycobacterium tuberculosis (Mtb) owes its success as a pathogen in large measure to its ability to exist in a persistent state of 'dormancy' resulting in a lifelong latent tuberculosis (TB) infection. An understanding of bacterial adaptation during dormancy will help in devising approaches to counter latent TB infection. In vitro models have provided valuable insights into bacterial adaptation; however, they have limitations because they do not disclose the bacterial response to the intracellular environment wherein the bacteria are simultaneously exposed to multiple stresses. We describe the pleiotropic response of Mtb in the vitamin C (vit C) model of dormancy developed in our laboratory. Vit C mediates a rapid regulation of genes representing ~14 % of the genome in Mtb cultures. The upregulated genes were better represented in lipid, intermediary metabolism and regulatory protein categories. The downregulated genes mainly related to virulence, detoxification, information pathways and cell wall processes. A comparison of this response to that in other models indicates that vit C generates a multiple-stress environment for axenic Mtb cultures that resembles a macrophage-like environment. The bacterial response to vit C resembles responses to gaseous stresses such as hypoxia and nitric oxide, oxidative and nitrosative stresses, nutrient starvation and, notably, the activated macrophage environment itself. These responses demonstrate that the influence of vit C on Mtb gene expression extends well beyond the DevR dormancy regulon. A detailed characterization of the response to vit C is expected to disclose useful strategies to counter the adaptive mechanisms essential to Mtb dormancy.
authors: Department of Biotechnology, All India Institute of Medical Sciences, New Delhi, India-110029.
authors: Kriti
authors: K
authors: Sikri
authors: Department of Biotechnology, All India Institute of Medical Sciences, New Delhi, India-110029.
authors: Sakshi Dhingra
authors: SD
authors: Batra
authors: Department of Biotechnology, All India Institute of Medical Sciences, New Delhi, India-110029.
authors: Malobi
authors: M
authors: Nandi
authors: Department of Biotechnology, All India Institute of Medical Sciences, New Delhi, India-110029.
authors: Priyanka
authors: P
authors: Kumari
authors: Department of Biotechnology, All India Institute of Medical Sciences, New Delhi, India-110029.
authors: Neetu Kumra
authors: NK
authors: Taneja
authors: Department of Biotechnology, All India Institute of Medical Sciences, New Delhi, India-110029 Centre for Biodesign and Diagnostics, Translational Health Science and Technology Institute, Gurgaon-122016, Haryana, India jstyagi@aiims.ac.in jstyagi@gmail.com.
authors: Jaya Sivaswami
authors: JS
authors: Tyagi
mesh_terms: D001205:Ascorbic Acid / Q000378:metabolism*; D001692:Biological Transport; D016000:Cluster Analysis; D004261:DNA Replication; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D006360:Heat-Shock Proteins / Q000378:metabolism; D008658:Inactivation, Metabolic; D050356:Lipid Metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000378:metabolism*; D009171:Mycolic Acids / Q000378:metabolism; D018384:Oxidative Stress; D014176:Protein Biosynthesis; D015203:Reproducibility of Results; D013312:Stress, Physiological; D014158:Transcription, Genetic
chemical_list: D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009171:Mycolic Acids; D001205:Ascorbic Acid