Summary of project PR002575
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002575. The data can be accessed directly via it's Project DOI: 10.21228/M8SV6X This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002575 |
| Project DOI: | doi: 10.21228/M8SV6X |
| Project Title: | A genome-scale metabolic model for deciphering the host metabolic perturbations during Mycobacterium tuberculosis infection |
| Project Type: | Metabolomics |
| Project Summary: | Conventional tuberculosis (TB) research predominantly relies on forward-designed experiments, such as studying host responses to Mycobacterium tuberculosis (Mtb) gene knockouts. While informative, these approaches offer only a partial view of host-pathogen interactions and often overlook the broader alterations in the host microenvironment during infection. To address this limitation, we adopted a backtracing strategy to retrospectively identify host metabolic modulators and link them to specific Mtb virulence factors. Using RNA-seq data from Mtb-infected mouse lung tissue, we integrated transcriptomic profiles into a genome-scale metabolic model to predict host metabolic genes essential for Mtb survival. This analysis identified 18 host proteins as putative modulators. We then constructed a host-pathogen protein interaction network, which connected these host factors to 9 Mtb proteins. Experimental validation using Mtb knockdown strains confirmed that three genes Rv1970, Rv0243, and Rv2234 play key roles in manipulating host responses rather than supporting intrinsic bacterial viability. Further, we employed targeted proteomics and untargeted metabolomics analyses on THP-1 macrophages infected with these KD strains to dissect the host-pathogen interaction mechanisms in greater detail. These findings in troduce a novel framework for decoding host-pathogen interactions and lay the groundwork for future host-directed therapy (HDT) strategies targeting Mtb-induced host vulnerabilities. |
| Institute: | Translational health science and technology institute |
| Department: | NCD |
| Laboratory: | Biomarker lab |
| Last Name: | Kumar |
| First Name: | Yashwant |
| Address: | NCR Biotech Science Cluster,, Faridabad, Haryana, 121001, India |
| Email: | y.kumar@thsti.res.in |
| Phone: | 01292876496 |
| Funding Source: | THSTI |
Summary of all studies in project PR002575
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST004099 | A genome-scale metabolic model for deciphering the host metabolic perturbations during Mycobacterium tuberculosis infection | Homo sapiens | Translational health science and technology institute | MS* | 2025-08-25 | 1 | 66 | Uploaded data (2.5G)* |
