Key Points
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Bacterial proteins can be damaged by oxidants that are present in the environment.
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Cys and Met residues are easily oxidized.
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Bacterial cells have a range of proteins that repair oxidized proteins.
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Thioredoxins (Trxs) and glutaredoxins (Grxs) repair oxidized cysteine residues.
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Methionine sulfoxide reductases (Msrs) repair oxidized methionine residues.
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Antioxidant defences are present in the bacterial cytoplasm and in extracytoplasmic compartments.
Abstract
Oxidative damage can have a devastating effect on the structure and activity of proteins, and may even lead to cell death. The sulfur-containing amino acids cysteine and methionine are particularly susceptible to reactive oxygen species (ROS) and reactive chlorine species (RCS), which can damage proteins. In this Review, we discuss our current understanding of the reducing systems that enable bacteria to repair oxidatively damaged cysteine and methionine residues in the cytoplasm and in the bacterial cell envelope. We highlight the importance of these repair systems in bacterial physiology and virulence, and we discuss several examples of proteins that become activated by oxidation and help bacteria to respond to oxidative stress.
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Acknowledgements
The authors thank members of the research groups of F.B. and J.F.C. for helpful discussions. A.G. is Chargée de Recherches and J.F.C. Maître de Recherche of the Fonds de la Recherche Scientifique-FNRS (F.R.S.-FNRS) and an Investigator of the Fonds de la Recherche Fondamentale Stratégique (FRFS)-WELBIO. This work was supported by grants from Centre National de la Recherche Scientifique (CNRS), Aix-Marseille Université, the A*MIDEX initiative and Fondation Recherche Médicale to F.B., and by the European Research Council (FP7/2007–2013) ERC independent researcher starting grant (282335–Sulfenic), the WELBIO and by grants from the F.R.S.-FNRS to J.F.C.
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Glossary
- Aerobic environments
-
Environments that are characterized by the presence of free molecular oxygen (O2).
- Univalent electron donors
-
Compounds that transfer electrons (one at a time) onto an electron acceptor.
- Metal centres
-
Metal atoms that are required for the structure or catalytic action of certain proteins.
- Dihydroflavin cofactors
-
(FADH2 cofactors). Reduced forms of flavin adenine dinucleotide (FAD), which is a covalently bound redox moiety that is required by certain oxidoreductases to exert their function.
- Quinones
-
Organic compounds that are composed of a polar redox-active head group coupled to a lipid side chain that varies in both length and degree of saturation. Quinones primarily function as electron transporters.
- Oxidants
-
Compounds that cause other molecules to lose electrons.
- Oxidation
-
A process in which electrons are lost by a molecule.
- Nucleophile
-
A chemical species that is attracted by a positive charge and is able to donate a pair of electrons.
- pKa
-
The negative logarithm of the acid dissociation constant (pKa = −log Ka). pKa is a quantitative measure of the strength of an acid in solution; the lower the pKa value, the stronger the acid.
- Deprotonation
-
The removal of a proton (a hydrogen cation (H+)) from an acid in an acid–base reaction. The species formed is the conjugate base of that acid.
- Thiolate
-
A deprotonated form of a thiol functional group.
- Electrophilic species
-
A chemical species that has affinity for electrons.
- Low-molecular-weight thiols
-
Highly reactive non-protein compounds that contain thiol functional groups (–SH), such as glutathione (GSH), mycothiol or bacillithiol.
- Diastereoisomeric forms
-
The forms adopted when a molecule has multiple chiral centres. Methionine sulfoxide (Met-O) contains two chiral centres: the α-carbon and the sulfur. Met-S-O and Met-R-O refer to the (S-) and (R-) configurations of the sulfur, respectively.
- Oxidoreductases
-
Enzymes that catalyse electron transfer from a donor (reductant) to an acceptor (oxidant).
- Reduction
-
A process in which electrons are gained by a molecule.
- Mixed-disulfide
-
An intermolecular covalent bridge (–S–S–) formed between two thiol groups from two different proteins or peptides.
- Iron–sulfur clusters
-
Inorganic prosthetic groups that are composed of iron and sulfur atoms, which can act as catalysts, redox sensors or structural elements.
- Glutathione
-
A major redox buffer. Glutathione reduces disulfide bonds by acting as an electron donor. Once oxidized, glutathione can be reduced by glutathione reductase, using nicotinamide adenine dinucleotide phosphate (NADPH) as an electron donor. Glutathione is composed of a tripeptide of L-cysteine, L-glutamate and glycine. In its oxidized form, two glutathione tripeptides are connected by a disulfide bond.
- Stereospecificity
-
A form of enzyme specificity, whereby an enzyme only catalyses its respective reaction if the substrate stereochemistry is correct.
- Redox potential
-
The measure (in volts) of the affinity of a compound for electrons.
- Oxidative stress
-
An imbalance between the production of oxidants, such as reactive oxygen species, and antioxidant defences
- Cytochrome b
-
A haem-containing membrane protein found in prokaryotic and eukaryotic cells that is involved in electron transport.
- Molybdopterin
-
A class of cofactors found in most molybdenum (Mo) and all tungsten (W) enzymes. Molybdopterin consists of a pyranopterin, which comprises two thiolates that function as ligands in molybdoenzymes and tungstoenzymes.
- Two-component system
-
A molecular system that is used by bacterial cells to sense and respond to signals through a phosphorylation cascade from a membrane receptor to a response regulator.
- Dithiothreitol
-
(DTT). A reducing agent that reduces disulfide bonds through a thiol–disulfide exchange reaction.
- Rcs phosphorelay
-
A complex signalling cascade that is used by enterobacteria to detect stress in the outer membrane and in the peptidoglycan layer.
- Cadmium
-
A non-redox-active metal that indirectly increases intracellular reactive oxygen species (ROS), primarily by binding to thiol groups, which leads to the inactivation of antioxidant defences, including scavenging enzymes and glutathione (GSH).
- Paraquat
-
A redox-cycling organic compound that is widely used as a source of oxygen radicals in laboratory experiments.
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Ezraty, B., Gennaris, A., Barras, F. et al. Oxidative stress, protein damage and repair in bacteria. Nat Rev Microbiol 15, 385–396 (2017). https://doi.org/10.1038/nrmicro.2017.26
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DOI: https://doi.org/10.1038/nrmicro.2017.26
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