Asset Details
Do you wish to reserve the book?
Bioenergetic reprogramming of macrophages reduces drug tolerance in Mycobacterium tuberculosis
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Bioenergetic reprogramming of macrophages reduces drug tolerance in Mycobacterium tuberculosis
Do you wish to request the book?
Bioenergetic reprogramming of macrophages reduces drug tolerance in Mycobacterium tuberculosis
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Bioenergetic reprogramming of macrophages reduces drug tolerance in Mycobacterium tuberculosis
2025
Overview
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 towards 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.
In
Mycobacterium tuberculosis
infection, both the bacterium and the macrophages exhibit phenotypic diversity. Here, the authors show that macrophage metabolic states control redox heterogeneity and drug response in intracellular
M. tuberculosis
.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/106
/ 13/31
/ 14/19
/ 38/90
/ 38/91
/ 64/60
/ Animals
/ Antitubercular Agents - pharmacology
/ Bacteria
/ Energy Metabolism - drug effects
/ Female
/ Humanities and Social Sciences
/ Humans
/ Mice
/ Mycobacterium tuberculosis - drug effects
/ Mycobacterium tuberculosis - genetics
/ Mycobacterium tuberculosis - metabolism
/ NF-E2-Related Factor 2 - genetics
/ NF-E2-Related Factor 2 - metabolism
/ Oxidation-Reduction - drug effects
/ Oxidative Phosphorylation - drug effects
/ Oxidative Stress - drug effects
/ Principal components analysis
/ Reactive Oxygen Species - metabolism
/ Science
