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  • Review Article
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Bacterial redox sensors

Nature Reviews Microbiology volume 2, pages 954–966 (2004)Cite this article

Key Points

  • Bacteria have sensitive and specific sensors — involving redox-active cofactors such as haem, flavins, pyridine nucleotides and iron–sulphur clusters, or redox-sensitive amino-acid side chains such as cysteine thiols — that monitor redox signals including oxygen, cytoplasmic redox state or the production of reactive oxygen species. Redox sensors control the processes that function to maintain redox homeostasis, usually at the level of transcription. This review explains the systems that have evolved to allow bacteria to sense and respond to different redox signals.

  • Thiol-based sensor function is reviewed. Typically, these sensors use cysteine modification to sense redox alterations. Examples include OxyR in Escherichia coli, the σR-RsrA system in Streptomyces coelicolor, CrtJ and the RegB–RegA in Rhodobacter sphaeroides, and OhrR from Bacillus subtilis.

  • The importance of Fe–S proteins in redox sensing is illustrated by the functions of several redox sensors from E. coli that use oxidation of Fe–S clusters to monitor the redox status of cell compartments and the environment to produce appropriate transcriptional responses — these include SoxR, Fnr, aconitase and IcsR.

  • Haem also functions to sample redox states in bacteria — examples include FixL in Sinorhizobium meliloti and Dos in E. coli, both of which function as oxygen sensors that coordinate the haem cofactor to a PAS (PER–ARNT–SIM) fold. By contrast, in B. subtilis the haem sensor is coordinated to a globin fold in the HemAT protein, which controls flagellar rotation in response to oxygen tension in chemotaxis.

  • Other redox sensors use the coenzymes FAD (flavin adenine dinucleotide) and FMN (flavin mononucleotide), which perceive redox states owing to their electron-carrying capacity. Those redox sensors reviewed here include the nitrogen-fixation regulation genes in Klebsiella pneumoniae, S. meliloti and Azotobacter vinelandii, and Aer, which mediates regulation of aerotaxis in E. coli.

  • Similarly, NAD cofactors can shuttle electrons and are used by regulators described in this review. Examples of such regulators include the Rex repressor in S. coelicolor, which monitors NAD status and respiratory activity according to oxygen availability and seems to be conserved among Gram-positive bacteria, and CbbR from the chemoautotroph Xanthobacter flavus, which samples whether there is enough reducing power available for carbon fixation.

  • Finally, the authors address the role of quinones in redox sensing. These cofactors might oxidize cysteines directly in the ArcB–ArcA system of E. coli that regulates gene expression under microaerobic and anaerobic growth conditions.

Abstract

Redox reactions pervade living cells. They are central to both anabolic and catabolic metabolism. The ability to maintain redox balance is therefore vital to all organisms. Various regulatory sensors continually monitor the redox state of the internal and external environments and control the processes that work to maintain redox homeostasis. In response to redox imbalance, new metabolic pathways are initiated, the repair or bypassing of damaged cellular components is coordinated and systems that protect the cell from further damage are induced. Advances in biochemical analyses are revealing a range of elegant solutions that have evolved to allow bacteria to sense different redox signals.

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Figure 1: Thiol-based redox switches.
Figure 2: Iron–sulphur cluster-based switches.
Figure 3: Haem-based switches.
Figure 4: Aer — a flavin cofactor-based redox sensor.
Figure 5: Comparison between the Rex and ArcB–ArcA redox sensors.

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Acknowledgements

Research in the author's laboratories is funded by the UK Biotechnology ad Biological Science Research Council and by the Wellcome Trust.

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Authors and Affiliations

  1. Department of Molecular Biology and Biotechnology, Krebs Institute for Biomolecular Research, University of Sheffield, Western Bank, Sheffield, S10 2TN, United Kingdom

    Jeffrey Green

  2. Department of Biochemistry, School of Life Sciences, University of Sussex, Falmer, BN1 9QG, Brighton, United Kingdom

    Mark S. Paget

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DATABASES

Swiss-Prot

σR

AcnA

AcnB

Aer

Arc

CbbR

Fnr

HemAT

NifA

NifL

OhrR

OxyR

Rex

SoxR

Glossary

REGULON

A group of transcriptional units or operons that are coordinately controlled by a regulator.

ANTIOXIDANT

A chemical that combines with free radicals and/or other chemicals that release free radicals that would otherwise damage molecules including DNA, RNA, lipids (fats) and proteins, and abnormally oxidize them.

FENTON REACTION

The reaction between Fe2+ and hydrogen peroxide that yields the highly reactive hydroxyl radical.

SIGMA FACTOR

The subunit of RNA polymerase holoenzyme that is required for promoter sequence recognition and the ability to initiate transcription.

ANTI-SIGMA FACTORS

A negative transcriptional regulator that functions by binding to a sigma factor and preventing its activity. An anti-anti-sigma factor, in turn, counteracts the action of an anti-sigma factor.

TWO-COMPONENT SYSTEM

A signal-transduction system using two components — a histidine protein kinase (HPK) and a response regulator — to sense and respond to external stimuli. HPK autophosphorylate at a histidyl residue following stimulation and transfer that phosphoryl group to a cognate response regulator at its aspartyl residue to induce a conformational change in the regulatory domain, which in turn activates an associated domain.

CUBIC

Refers to the symmetry of a cluster, where cubic is three dimensional and planar is two dimensional.

PLANAR

Two-dimensional arrangement of molecules in a motif.

APO

Inactive form of a regulatory protein or enzyme.

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Green, J., Paget, M. Bacterial redox sensors. Nat Rev Microbiol 2, 954–966 (2004). https://doi.org/10.1038/nrmicro1022

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