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.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Mehrotra P,Jamwal SV,Saquib N,Sinha N,Siddiqui Z,Manivel V,Chatterjee S,Rao KV

doi

10.1371/journal.ppat.1004265

subject

Has Abstract

pub_date

2014-07-24 00:00:00

pages

e1004265

issue

7

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-14-00637

journal_volume

10

pub_type

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