Review
Regulators of oxidative stress response genes in Escherichia coli and their functional conservation in bacteria

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Abstract

Oxidative stress, through the production of reactive oxygen species, is a natural consequence of aerobic metabolism. Escherichia coli has several major regulators activated during oxidative stress, including OxyR, SoxRS, and RpoS. OxyR and SoxR undergo conformation changes when oxidized in the presence of hydrogen peroxide and superoxide radicals, respectively, and subsequently control the expression of cognate genes. In contrast, the RpoS regulon is induced by an increase in RpoS levels. Current knowledge regarding the activation and function of these regulators and their dependent genes in E. coli during oxidative stress forms the scope of this review. Despite the enormous genomic diversity of bacteria, oxidative stress response regulators in E. coli are functionally conserved in a wide range of bacterial groups, possibly reflecting positive selection of these regulators. SoxRS and RpoS homologs are present and respond to oxidative stress in Proteobacteria, and OxyR homologs are present and function in H2O2 resistance in a range of bacteria, from gammaproteobacteria to Actinobacteria. Bacteria have developed complex, adapted gene regulatory responses to oxidative stress, perhaps due to the prevalence of reactive oxygen species produced endogenously through metabolism or due to the necessity of aerotolerance mechanisms in anaerobic bacteria exposed to oxygen.

Highlights

► Major oxidative stress regulators in Escherichia coli are OxyR, SoxRS, and RpoS. ► OxyR and SoxRS regulons are expressed after activation of regulators by ROS. ► Functional conservation of OxyR is evident from Proteobacteria to Actinobacteria. ► SoxRS and RpoS are functionally conserved in Proteobacteria. ► Other oxidative stress regulators include Fur, NorR, and IscR.

Section snippets

Oxidative stress in bacteria

Bacteria, under aerobic conditions, experience oxidative stress through the formation of reactive oxygen species (ROS)1 that can damage several cellular sites, including iron-sulfur clusters, cysteine and methionine protein residues, and DNA [1], [2]. ROS are an inevitable by-product of oxygen exposure and utilization. For example, superoxide

OxyR, principal regulator for hydrogen peroxide detoxification

OxyR, a 34 kDa protein that forms a homotetramer [8], is a homolog of the LysR family of transcriptional regulators in E. coli [9], [10], and characteristic of this protein family [11], OxyR negatively regulates expression from its encoding gene, oxyR, and positively regulates an adjacent small RNA gene, oxyS [12]. OxyR controls a regulon of almost 40 genes, which protect the cell from hydrogen peroxide toxicity (Table 1). Consequently, oxyR mutants are hypersensitive to H2O2, and constitutive

Concluding remarks

Oxidative stress responses coordinated by specific regulators ensure bacterial survival during episodic exposure to exogenous ROS or to ROS generated as a consequence of normal respiration. Oxidative stress regulators, such as OxyR and RpoS, can modulate expression of one another and, in some circumstances, control expression of the same regulon members. OxyR, present in Proteobacteria, Bacteroidetes, and Actinobacteria, is likely of an earlier evolutionary origin than SoxRS and RpoS, which are

Acknowledgments

We thank T. Dong for critical review of this manuscript. This study was supported by a research Grant from the Natural Sciences and Engineering Research Council of Canada (NSERC) to H.E.S. S.M.C. was partially supported by an Ontario Graduate Scholarship.

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