Metabolic rewiring of macrophages may shorten tuberculosis treatment

The Hindu
The Hindu
5m ago
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Modulating macrophage metabolism to glycolysis raises oxidative stress and reduces TB bacteria drug tolerance, enabling shorter treatment in mice models.
Metabolic rewiring of macrophages may shorten tuberculosis treatment
A What happened
Tuberculosis bacteria survive within macrophages by enduring oxidative stress, sustaining drug tolerance that extends treatment duration. Researchers found macrophages relying on glycolysis generate higher oxidative stress, weakening bacteria. Inhibiting NRF2 protein prompted this metabolic switch. Meclizine, a common drug, induced glycolysis in infected macrophages, enhancing antibiotic effectiveness and reducing bacterial load significantly in mice. This host-directed approach provides an adjunctive TB therapy route, potentially shortening treatment and improving patient outcomes. Further clinical studies are needed to confirm safety and efficacy in humans and optimal drug combinations to prevent relapse and address drug resistance challenges.
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Key insights

  • 1

    Host metabolism shapes drug tolerance: The metabolic state of the host macrophage directly alters Mycobacterium tuberculosis' ability to tolerate antibiotics, indicating host-cell factors are critical in infection persistence and treatment outcomes.

  • 2

    Targeting NRF2 modulates bacterial susceptibility: NRF2 supports a drug-tolerant niche by maintaining oxidative phosphorylation and low oxidative stress. Inhibiting NRF2 shifts macrophages to glycolysis and oxidative stress, enhancing bacterial drug sensitivity.

  • 3

    Repurposing meclizine for TB therapy: Meclizine’s ability to shift macrophage metabolism toward glycolysis shows promise as an adjunct to standard TB drugs, potentially shortening treatments and reducing bacterial persistence without directly targeting bacteria, lowering resistance risk.

Takeaways

Reprogramming macrophage metabolism to enhance oxidative stress provides a promising strategy to improve TB drug efficacy and shorten treatment duration. Clinical trials are needed to assess meclizine's role in human therapy.

Topics

Science & Research Biology Medical Research Health & Medicine Pharma & Biotech