The mechanism of redox sensing in Mycobacterium tuberculosis

• Published in: Free radical biology & medicine 2012-10, Vol.53 (8), p.1625-1641
• Main Authors: Bhat, Shabir Ahmad, Singh, Nisha, Trivedi, Abhishek, Kansal, Pallavi, Gupta, Pawan, Kumar, Ashwani
• Format: Article
• Language: English
• Subjects: Animals; Anti-σ factors; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; carbon monoxide; disease outbreaks; DosR; DosS; DosT; Free radicals; Gene Expression Regulation, Bacterial; genome; homeostasis; Humans; hypoxia; Metabolic flexibility; Mycobacterium tuberculosis; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - pathogenicity; nitric oxide; Oxidation-Reduction; Oxidative Stress; pathogenesis; pathogens; proteins; Redox homeostasis; Redox sensing; Serine–threonine kinases; tuberculosis; Tuberculosis - metabolism; Tuberculosis - microbiology; Tuberculosis - pathology; Virulence; WhiB3
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2012.08.008

Tuberculosis epidemics have defied constraint despite the availability of effective treatment for the past half-century. Mycobacterium tuberculosis, the causative agent of TB, is continually exposed to a number of redox stressors during its pathogenic cycle. The mechanisms used by Mtb to sense redox stress and to maintain redox homeostasis are central to the success of Mtb as a pathogen. Careful analysis of the Mtb genome has revealed that Mtb lacks classical redox sensors such as FNR, FixL, and OxyR. Recent studies, however, have established that Mtb is equipped with various sophisticated redox sensors that can detect diverse types of redox stress, including hypoxia, nitric oxide, carbon monoxide, and the intracellular redox environment. Some of these sensors, such as heme-based DosS and DosT, are unique to mycobacteria, whereas others, such as the WhiB proteins and anti-σ factor RsrA, are unique to actinobacteria. This article provides a comprehensive review of the literature on these redox-sensory modules in the context of TB pathogenesis. [Display omitted] ► The role of redox stress in tuberculosis pathogenesis is reviewed. ► Classical redox sensors and Mycobacterium tuberculosis are discussed. ► We also discuss the mechanism of redox sensing by heme-based redox sensors in Mycobacterium. ► The role of iron–sulfur cluster proteins in the regulation of redox homeostasis is examined. ► Redox sensing by σ factors and serine/threonine kinases is also reviewed.