Format

Send to

Choose Destination
Sci Rep. 2018 Mar 22;8(1):5079. doi: 10.1038/s41598-018-22884-8.

System-wide coordinates of higher order functions in host-pathogen environment upon Mycobacterium tuberculosis infection.

Author information

1
C R Rao AIMSCS, University of Hyderabad campus, Hyderabad, Telangana, India.
2
IOB-YU Centre for Systems Biology and Molecular Medicine, Yenepoya Research Centre Yenepoya University, Mangalore, Karnataka, India.
3
Centre for Computational Biology and Bioinformatics, School of Life Sciences, Central University of Himachal Pradesh, Dharamshala, India.
4
Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad, India.
5
Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow, Uttar Pradesh, 226025, India.
6
IOB-YU Centre for Systems Biology and Molecular Medicine, Yenepoya Research Centre Yenepoya University, Mangalore, Karnataka, India. bio.sailu@gmail.com.

Abstract

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.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center