System-wide coordinates of higher order functions in host-pathogen environment upon Mycobacterium tuberculosis infection
Molecular signatures and their interactions behind the successful establishment of infection of Mycobacterium tuberculosis ( Mtb ) inside macrophage are largely unknown. In this work, we present an inter-system scale atlas of the gene expression signatures, their interactions and higher order gene f...
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Veröffentlicht in: | Scientific reports 2018-03, Vol.8 (1), p.5079-12, Article 5079 |
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Sprache: | eng |
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Zusammenfassung: | Molecular signatures and their interactions behind the successful establishment of infection of
Mycobacterium tuberculosis
(
Mtb
) inside macrophage are largely unknown. In this work, we present an inter-system scale atlas of the gene expression signatures, their interactions and higher order gene functions of macrophage-
Mtb
environment at the time of infection. We have carried out large-scale meta-analysis of previously published gene expression microarray studies andhave identified a ranked list of differentially expressed genes and their higher order functions in intracellular
Mtb
as well as the infected macrophage. Comparative analysis of gene expression signatures of intracellular
Mtb
with the
in vitro
dormant
Mtb
at different hypoxic and oxidative stress conditions led to the identification of the large number of
Mtb
functional groups, namely operons, regulons and pathways that were common and unique to the intracellular environment and dormancy state. Some of the functions that are specific to intracellular
Mtb
are cholesterol degradation and biosynthesis of immunomodulatory phenolic compounds. The molecular signatures we have identified to be involved in adaptation to different stress conditions in macrophage environment may be critical for designing therapeutic interventions against tuberculosis. And, our approach may be broadly applicable for investigating other host-pathogen interactions. |
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ISSN: | 2045-2322 2045-2322 |
DOI: | 10.1038/s41598-018-22884-8 |