Thiol-Based Redox Mechanisms in Bacterial Stress Responses

Bacteria rely on finely tuned thiol-based redox systems to detect and counteract environmental and host‐derived stresses. Central to these systems are low molecular weight thiols such as glutathione, bacillithiol and mycothiol, which serve as redox buffers and protect against oxidative damage by reactive oxygen, nitrogen and chlorine species. Under stress, cysteine residues in sensor proteins undergo reversible modifications, including mixed disulfide formation and sulfenic acid conversion, triggering conformational changes that regulate transcriptional responses and enzymatic detoxification pathways. Key regulatory proteins, such as MarR‐ and PerR‐family repressors, employ thiol switches to control the expression of antioxidant enzymes, repair systems and metal‐homeostasis factors. Concurrently, dedicated oxidoreductases and thiol‐disulfide oxidoreductases restore thiol homeostasis by reducing protein disulfides and regenerating low molecular weight thiols. Together, these interconnected processes enable bacteria to withstand fluctuating redox challenges, maintain metabolic integrity and, in the case of pathogens, survive host immune attacks. The global significance of this research spans environmental microbiology, industrial biotechnology and the development of novel antimicrobial strategies targeting redox vulnerabilities.

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Thiol-Based Redox Mechanisms in Bacterial Stress Responses publication trend

The graph below shows the total number of articles in thiol-based redox mechanisms in bacterial stress responses across all publications each year (not limited to Nature Index journals).

Technical terms

Thiol: An organic compound containing a sulphydryl (–SH) group, critical for redox buffering and protein regulation.

Redox buffer: A molecule, such as glutathione or bacillithiol, that maintains cellular redox balance by reversible oxidation and reduction.

S-thiolation: Reversible formation of a mixed disulfide between a protein cysteine residue and a low molecular weight thiol, protecting against overoxidation.

Low molecular weight (LMW) thiols: Small thiol compounds, including glutathione, bacillithiol and mycothiol, that serve as key redox regulators in bacteria.

Thiol switch: A cysteine‐based mechanism in sensor proteins where oxidation or modification alters protein activity and gene expression.

References

1. Metabolic turnover of cysteine-related thiol compounds at environmentally relevant concentrations by Geobacter sulfurreducens. Frontiers in Microbiology (2023).
2. Reduce, Induce, Thrive: Bacterial Redox Sensing during Pathogenesis. Journal of Bacteriology (2018).
3. Redox regulation by reversible protein S-thiolation in bacteria. Frontiers in Microbiology (2015).
4. S-Bacillithiolation Protects Against Hypochlorite Stress in Bacillus subtilis as Revealed by Transcriptomics and Redox Proteomics*. Molecular & Cellular Proteomics (2011).
5. Crystal Structures of the Reduced, Sulfenic Acid, and Mixed Disulfide Forms of SarZ, a Redox Active Global Regulator in Staphylococcus aureus *. Journal of Biological Chemistry (2009).
6. New roles for glutathione: Modulators of bacterial virulence and pathogenesis. Redox Biology (2021).
7. Staphylococcus aureus Uses the Bacilliredoxin (BrxAB)/Bacillithiol Disulfide Reductase (YpdA) Redox Pathway to Defend Against Oxidative Stress Under Infections. Frontiers in Microbiology (2019).