The role of thioredoxin system in the maintenance of redox homeostasis in Mycobacterium tuberculosis

Maintenance of intracellular redox homeostasis is pivotal for the survival of an organism. During intricate host–pathogen interactions, pathogens typically encounter a barrage of oxidative assault from the host. Therefore, the successful evasion of the pathogen from the hostile environment relies on the efficiency of its redox response system. Mycobacterium tuberculosis, the etiological agent of tuberculosis, confronts redox imbalance mediated by reactive oxygen species (ROS) and reactive nitrogen species (RNS), as well as hypoxic conditions within the host. This review focuses on the survival strategies employed by M. tuberculosis in the redox-imbalanced environment of the host. The initial section of this review centers on the thioredoxin system of M. tuberculosis, which encompasses thioredoxin reductase along with thioredoxins (TrxB and TrxC). Various physiological targets of thioredoxins and the strategies employed to modulate them are described. The subsequent section of this review addresses multiple aspects of hypoxic conditions encountered by M. tuberculosis within the granuloma. This section delineates factors involved in the regulation of hypoxia, such as Rv0081, a transcriptional hub protein, and GroEL1, a chaperone protein. The collective information presented here offers a concise overview of the redox systems of M. tuberculosis that enable it to cope with oxidative stress (primarily the thioredoxin system) and hypoxia.