Summary of project PR002596
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 PR002596. The data can be accessed directly via it's Project DOI: 10.21228/M8355F This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002596 |
| Project DOI: | doi: 10.21228/M8355F |
| Project Title: | Bioenergetic reprogramming of macrophages reduces drug tolerance in Mycobacterium tuberculosis |
| Project Type: | Research |
| Project Summary: | Effective clearance of Mycobacterium tuberculosis (Mtb) requires targeting drug-tolerant populations within host macrophages. Here, we show that macrophage metabolic states govern redox heterogeneity and drug response in intracellular Mtb. Using a redox-sensitive fluorescent reporter (Mrx1-roGFP2), flow cytometry, and transcriptomics, we found that macrophages with high oxidative phosphorylation (OXPHOS) and low glycolysis harbor reductive, drug-tolerant Mtb, whereas glycolytically active macrophages generate mitochondrial ROS via reverse electron transport, imposing oxidative stress on Mtb and enhancing drug efficacy. Computational and genetic analyses identified Nrf2 as a key regulator linking host metabolism to bacterial redox state and drug tolerance. Pharmacological reprogramming of macrophages with the FDA-approved drug meclizine (MEC) shifted metabolism toward glycolysis, suppressed redox heterogeneity, and reduced Mtb drug tolerance in macrophages and mice. MEC exhibited no adverse interactions with frontline anti-TB drugs. These findings demonstrate the therapeutic potential of host metabolic reprogramming to overcome Mtb drug tolerance. |
| Institute: | Indian Institute of Science |
| Department: | Microbiology and Cell Biology |
| Last Name: | Singh |
| First Name: | Amit |
| Address: | Centre for Infectious Disease Research, Bangalore, Karnataka, 560012, India |
| Email: | common.aslab@gmail.com |
| Phone: | +918022933273 |
Summary of all studies in project PR002596
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST004129 | Metabolomic analysis of TCA cycle intermediates in Mycobacterium tuberculosis-infected BMDMs. | Mus musculus | Indian Institute of Science | MS | 2025-08-22 | 1 | 15 | Uploaded data (2.9M)* |
| ST004134 | Metabolomic analysis of glycolytic intermediates in Mycobacterium tuberculosis-infected BMDMs (Bone marrow-derived macrophages) | Mus musculus | Indian Institute of Science | MS | 2025-08-22 | 1 | 13 | Uploaded data (1.9M)* |
