Pathogenicity of Mycobacterium tuberculosis Is Expressed by Regulating Metabolic Thresholds of the Host Macrophage

PLoS Pathogens

NajmuddinSaquib¹  Kanury V. S. Rao¹  Zaved Siddiqui¹  Shilpa V. Jamwal¹  Neeraj Sinha¹  Venkatasamy Manivel¹  Parul Mehrotra¹  Samrat Chatterjee¹ 

[1] Immunology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India

关键词: Macrophages;    Glucose;    Mycobacterium tuberculosis;    Apoptosis;    Metabolic labeling;    Host cells;    Cell metabolism;    Glucose metabolism;   

DOI  :  10.1371/journal.ppat.1004265

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY