title: Pathogenicity of Mycobacterium tuberculosis is expressed by regulating metabolic thresholds of the host macrophage.
abstract: The success of Mycobacterium tuberculosis as a pathogen derives from its facile adaptation to the intracellular milieu of human macrophages. To explore this process, we asked whether adaptation also required interference with the metabolic machinery of the host cell. Temporal profiling of the metabolic flux, in cells infected with differently virulent mycobacterial strains, confirmed that this was indeed the case. Subsequent analysis identified the core subset of host reactions that were targeted. It also elucidated that the goal of regulation was to integrate pathways facilitating macrophage survival, with those promoting mycobacterial sustenance. Intriguingly, this synthesis then provided an axis where both host- and pathogen-derived factors converged to define determinants of pathogenicity. Consequently, whereas the requirement for macrophage survival sensitized TB susceptibility to the glycemic status of the individual, mediation by pathogen ensured that the virulence properties of the infecting strain also contributed towards the resulting pathology.
authors: Immunology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
authors: Parul
authors: P
authors: Mehrotra
authors: Immunology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
authors: Shilpa V
authors: SV
authors: Jamwal
authors: Immunology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
authors: Najmuddin
authors: N
authors: Saquib
authors: Immunology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
authors: Neeraj
authors: N
authors: Sinha
authors: Immunology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
authors: Zaved
authors: Z
authors: Siddiqui
authors: Immunology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
authors: Venkatasamy
authors: V
authors: Manivel
authors: Immunology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
authors: Samrat
authors: S
authors: Chatterjee
authors: Immunology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
authors: Kanury V S
authors: KV
authors: Rao
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D005260:Female; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics*; D006801:Humans; D008264:Macrophages / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D014376:Tuberculosis / Q000235:genetics / Q000378:metabolism; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors