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Understanding the role of interactions between host and Mycobacterium tuberculosis under hypoxic condition: an in silico approach.

ABSTRACT: BACKGROUND:Mycobacterium tuberculosis infection in humans is often associated with extended period of latency. To adapt to the hostile hypoxic environment inside a macrophage, M. tuberculosis cells undergo several physiological and metabolic changes. Previous studies have mostly focused on inspecting individual facets of this complex process. In order to gain deeper insights into the infection process and to understand the coordination among different regulatory/ metabolic pathways in the pathogen, the current in silico study investigates three aspects, namely, (i) host-pathogen interactions (HPIs) between human and M. tuberculosis proteins, (ii) gene regulatory network pertaining to adaptation of M. tuberculosis to hypoxia and (iii) alterations in M. tuberculosis metabolism under hypoxic condition. Subsequently, cross-talks between these components have been probed to evaluate possible gene-regulatory events as well as HPIs which are likely to drive metabolic changes during pathogen's adaptation to the intra-host hypoxic environment. RESULTS:The newly identified HPIs suggest the pathogen's ability to subvert host mediated reactive oxygen intermediates/ reactive nitrogen intermediates (ROI/ RNI) stress as well as their potential role in modulating host cell cycle and cytoskeleton structure. The results also indicate a significantly pronounced effect of HPIs on hypoxic metabolism of M. tuberculosis. Findings from the current study underscore the necessity of investigating the infection process from a systems-level perspective incorporating different facets of intra-cellular survival of the pathogen. CONCLUSIONS:The comprehensive host-pathogen interaction network, a Boolean model of M. tuberculosis H37Rv (Mtb) hypoxic gene-regulation, as well as a genome scale metabolic model of Mtb, built for this study are expected to be useful resources for future studies on tuberculosis infection.

SUBMITTER: Bose T

PROVIDER: S-EPMC6064076 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Understanding the role of interactions between host and Mycobacterium tuberculosis under hypoxic condition: an in silico approach.

Bose Tungadri T Das Chandrani C Dutta Anirban A Mahamkali Vishnuvardhan V Sadhu Sudipta S Mande Sharmila S SS

BMC genomics 20180727 1

<h4>Background</h4>Mycobacterium tuberculosis infection in humans is often associated with extended period of latency. To adapt to the hostile hypoxic environment inside a macrophage, M. tuberculosis cells undergo several physiological and metabolic changes. Previous studies have mostly focused on inspecting individual facets of this complex process. In order to gain deeper insights into the infection process and to understand the coordination among different regulatory/ metabolic pathways in th ...[more]

PMID: 30053801

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Project description:Climate change affects animal physiology. In particular, rising ambient temperatures reduce animal vitality due to heat stress and this can be observed at various levels which included genome, transcriptome, and microbiome. In a previous study, microbiota highly associated with changes in cattle physiology, which included rectal temperature, drooling score and respiratory score, were identified under heat stress conditions. In the present study, genes differentially expressed between individuals were selected representing different additive genetic effects toward the heat stress response in cattle in their production condition. Moreover, a correlation network analysis was performed to identify interactions between the transcriptome and microbiome for 71 Chinese Holstein cows sequenced for mRNA from blood samples and for 16S rRNA genes from fecal samples. Bioinformatics analysis was performed comprising: i) clustering and classification of 16S rRNA sequence reads, ii) mapping cows' transcripts to the reference genome and their expression quantification, and iii) statistical analysis of both data types-including differential gene expression analysis and gene set enrichment analysis. A weighted co-expression network analysis was carried out to assess changes in the association between gene expression and microbiota abundance as well as to find hub genes/microbiota responsible for the regulation of gene expression under heat stress. Results showed 1,851 differentially expressed genes were found that were shared by three heat stress phenotypes. These genes were predominantly associated with the cytokine-cytokine receptor interaction pathway. The interaction analysis revealed three modules of genes and microbiota associated with rectal temperature with which two hubs of those modules were bacterial species, demonstrating the importance of the microbiome in the regulation of gene expression during heat stress. Genes and microbiota from the significant modules can be used as biomarkers of heat stress in cattle.

Dataset Information

Understanding the role of interactions between host and Mycobacterium tuberculosis under hypoxic condition: an in silico approach.

Publications

Understanding the role of interactions between host and Mycobacterium tuberculosis under hypoxic condition: an in silico approach.

Similar Datasets

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