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The molecular mechanisms and physiological consequences of oxidative stress: lessons from a model bacterium

Nature Reviews Microbiology volume 11, pages 443–454 (2013)Cite this article

Subjects

Key Points

  • Excess oxygen can disrupt the growth of most organisms, but the underlying mechanisms of damage have proved difficult to unravel. The model bacterium Escherichia coli represents the best understood organism in terms of the effects of and response to oxidative stress.

  • Superoxide (O2−) and hydrogen peroxide (H2O2) are formed within cells when molecular oxygen (O2) adventitiously acquires electrons from the reduced cofactors of flavoproteins.

  • Both O2− and H2O2 can oxidize the exposed Fe–S clusters of a family of dehydratases. This event destabilizes the clusters, and their consequent disintegration eliminates enzyme activity.

  • O2− and H2O2 also inactivate a variety of non-redox enzymes that use single Fe2+ ions as catalytic cofactors.

  • DNA is damaged when H2O2 reacts with the intracellular pool of unincorporated iron. The iron that is released from oxidized metalloproteins enlarges this pool and accelerates this process.

  • The transcription factor OxyR detects modest increments in intracellular H2O2. It activates several responses that help preserve the activities of Fe–S and mononuclear metalloenzymes.

  • The SoxRS system detects redox-active compounds that are released by plants and some bacteria. These compounds can generate toxic doses of O2−, and the SoxRS system acts primarily to minimize the amounts of these compounds inside the cell.

  • Future studies should aim to determine whether the knowledge gained from studying oxidative stress in the facultative anaerobe E. coli is applicable to other organisms, such as strictly aerobic and microaerophilic bacteria.

Abstract

Oxic environments are hazardous. Molecular oxygen adventitiously abstracts electrons from many redox enzymes, continuously forming intracellular superoxide and hydrogen peroxide. These species can destroy the activities of metalloenzymes and the integrity of DNA, forcing organisms to protect themselves with scavenging enzymes and repair systems. Nevertheless, elevated levels of oxidants quickly poison bacteria, and both microbial competitors and hostile eukaryotic hosts exploit this vulnerability by assaulting these bacteria with peroxides or superoxide-forming antibiotics. In response, bacteria activate elegant adaptive strategies. In this Review, I summarize our current knowledge of oxidative stress in Escherichia coli, the model organism for which our understanding of damage and defence is most well developed.

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Figure 1: The generation of reactive oxygen species and the enzymes used for scavenging.
Figure 2: Activation of redox-sensitive transcriptional regulators in Escherichia coli.
Figure 3: The role and oxidative vulnerability of dehydratase [4Fe–4S] clusters.
Figure 4: The role and oxidative vulnerability of mononuclear iron enzymes.
Figure 5: Overview of damage caused by reactive oxygen species in Escherichia coli.

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Acknowledgements

The author is grateful to past and current members of his laboratory who have contributed to many of the ideas in this Review. Work in the author's laboratory is currently supported by grants GM49640 and GM101012 from the US National Institutes of Health.

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  1. Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA

    James A. Imlay

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Glossary

Reduced

With a lower oxidation state, typically as a result of acceptance of an electron from another molecule or atom.

Spin-aligned electrons

Electrons that are in separate orbitals and have the same spin quantum number. Two electrons must have opposite spins to reside in the same orbital.

Reduction potential

The measure of the thermodynamic affinity of a compound for an electron.

Metal centres

Metal atoms that confer structure and/or catalytic function on a protein. Redox enzymes commonly use the transition metals iron, copper, manganese, molybdenum, nickel and selenium for electron transfer reactions.

Flavins

Organic cofactors that bind to redox enzymes in the form of FAD or flavin mononucleotide (FMN). These cofactors are commonly used to mediate electron exchange between divalent electron donors and univalent acceptors.

Respiratory quinones

Lipid-soluble organic molecules that carry electrons between membrane-bound redox enzymes.

Autoxidation

Electron transfer from a reduced enzyme or cofactor to molecular oxygen.

Hyperoxia

Molecular oxygen concentrations above that of air (22%).

Thiol-based peroxidase

An enzyme that uses a redox-active Cys residue to reduce hydrogen peroxide to water.

RpoS system

The regulon that is governed by RNA polymerase σ–factor RpoS. RpoS is activated in stationary phase and under many stress conditions that suppress growth.

Chromophores

Light-absorbing compounds.

Michael acceptors

Unsaturated carbonyl compounds that are vulnerable to addition reactions by nucleophiles.

Lewis acid

A molecular moiety that can share an electron pair provided by a donor compound.

Half-time

In an exponential decay process, the time needed for conversion of half of the reactant to product.

Isc system

(Fe–S cluster synthesis system). A multiprotein complex that assembles Fe–S clusters on a scaffold protein and then transfers them to client proteins.

Suf system

A protein complex that assembles and transfers Fe–S clusters to recipient proteins. The Suf system comprises different proteins to the Fe–S cluster synthesis (Isc) system, and the activity of the Suf system is more resistant than that of the Isc system to chemical stress and iron deficiency.

SOS system

The global response to DNA damage that is exhibited by many bacteria.

Peroxidation

Lipid damage in which peroxyl groups are added to unsaturated bonds, thereby disrupting lipid packing in the membrane.

Redoxins

Proteins that use their Cys residues to deliver electrons to oxidants. Thioredoxins and glutaredoxins reduce disulphide bonds in cellular proteins.

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Imlay, J. The molecular mechanisms and physiological consequences of oxidative stress: lessons from a model bacterium. Nat Rev Microbiol 11, 443–454 (2013). https://doi.org/10.1038/nrmicro3032

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