Redox Homeostasis in Mycobacterial Pathogenesis

Infection by Mycobacterium species demands a finely tuned redox equilibrium that underpins both bacterial survival and virulence within the host. Mycobacteria face multifaceted oxidative challenges, including reactive oxygen and nitrogen species generated by phagocytic cells, and adapt through a suite of thiol-based buffers and enzymatic pathways. Central to this adaptation is mycothiol, the predominant low-molecular-weight thiol that maintains cytoplasmic redox potential and facilitates detoxification of electrophiles. Integral enzymes such as thioredoxin reductases and components of the iron-sulfur cluster biogenesis machinery further regulate redox poise, ensuring proper folding of Fe-S proteins and safeguarding cellular processes from oxidative damage. Moreover, specialised transcriptional regulators sense redox perturbations and orchestrate adaptive gene expression responses. Advances in real-time imaging and chemical perturbation have revealed heterogeneity in intrabacterial redox states, linking redox dynamics to antibiotic susceptibility and persistence. Understanding these intersecting pathways illuminates new avenues for therapeutic intervention, targeting redox vulnerabilities to enhance antimycobacterial efficacy and limit disease transmission.

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Redox Homeostasis in Mycobacterial Pathogenesis publication trend

The graph below shows the total number of articles in redox homeostasis in mycobacterial pathogenesis across all publications each year (not limited to Nature Index journals).

Technical terms

Redox homeostasis: Balance between reduction and oxidation reactions that maintains cellular function and viability.

Mycothiol (MSH): Principal low-molecular-weight thiol in mycobacteria, acting as a major cytoplasmic redox buffer and detoxifying agent.

Reactive oxygen species (ROS): Chemically reactive molecules derived from oxygen, including superoxide and hydrogen peroxide, which can inflict oxidative damage.

Iron-sulfur (Fe-S) cluster: Cofactor composed of iron and sulfur atoms that is essential for the function of many enzymes and redox proteins.

Redox-sensitive biosensor: Genetically encoded probe that reports real-time redox changes via fluorescence, enabling noninvasive monitoring of intracellular redox potential.

References

1. The Response of Mycobacterium Tuberculosis to Reactive Oxygen and Nitrogen Species. Frontiers in Microbiology (2011).
2. Characterization of a Novel Oxidative Stress Responsive Transcription Regulator in Mycobacterium bovis. Biomedicines (2024).
3. Genome mining of Mycobacterium tuberculosis: targeting SufD as a novel drug candidate through in silico characterization and inhibitor screening. Frontiers in Microbiology (2024).
4. Reengineering Redox Sensitive GFP to Measure Mycothiol Redox Potential of Mycobacterium tuberculosis during Infection. PLOS Pathogens (2014).
5. Mycobacterium tuberculosis Thioredoxin Reductase Is Essential for Thiol Redox Homeostasis but Plays a Minor Role in Antioxidant Defense. PLOS Pathogens (2016).