Targeting Oxidative Stress Pathways for Improved Tuberculosis Treatment Outcomes
DOI:
https://doi.org/10.33003/fjs-2026-1019-6181Keywords:
Oxidative stress, Mycobacterium tuberculosis, Drug resistance, Redox regulators, Host-directed therapyAbstract
Tuberculosis (TB) treatment remains challenged by prolonged therapy, drug resistance, and host–pathogen interactions driven by oxidative stress. This review examines oxidative stress not as a uniformly pathogenic process but as a cause, consequence, and mediator of TB pathology, drug response, and therapeutic outcome in Mycobacterium tuberculosis infection. Reactive oxygen and nitrogen species (ROS/RNS) generated by host phagocytes contribute to antimicrobial activity and are integral to the activation of key anti-TB prodrugs such as isoniazid and pyrazinamide. However, excessive or sustained oxidative stress promotes bacterial adaptation through redox-sensitive regulators, including SigH and WhiB7, which enhance antioxidant defences, efflux pump activity, and phenotypic persistence, and may contribute to, but do not alone determine, disease reactivation. Host redox imbalance, exacerbated by comorbidities such as diabetes and HIV, further impairs drug efficacy and increases toxicity. Emerging host-directed therapies, including N-acetylcysteine, glutathione supplementation, and Nrf2 modulators, aim to restore redox homeostasis and improve treatment outcomes. Targeting the oxidative stress–resistance axis therefore represents a promising, though still evolving, strategy for combating multidrug-resistant tuberculosis and optimising therapeutic success.
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