Defining the binding determinants of Shewanella oneidensis OxyR: Implications for the link between the contracted OxyR regulon and adaptation

Wan, Fen; Kong, Linggen; Gao, Haichun

doi:10.1074/jbc.ra117.001530

Cited by 23 publications

(44 citation statements)

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“…The first model is that loss of oxyR induces the upregulation of oxyRindependent pathways that lead to increased transcription of hydrogen peroxide detoxification genes. The second model is that OxyR has a dual function as both a repressor and an activator of ahpF1, ahpF2, and katE depending on the oxidation state of OxyR, which has been proposed previously for OxyR in other organisms, including N. meningitidis and S. oneidensis (30,59). In this dual repressor-activator model, reduced OxyR binding to the promoter represses transcription and oxidized OxyR binding to the promoter activates transcription.…”

Section: Discussionmentioning

confidence: 91%

Acinetobacter baumanniiOxyR Regulates the Transcriptional Response to Hydrogen Peroxide

et al. 2019

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Acinetobacter baumanniiis a Gram-negative opportunistic pathogen that causes diverse infections, including pneumonia, bacteremia, and wound infections. Due to multiple intrinsic and acquired antimicrobial-resistance mechanisms,A. baumanniiisolates are commonly multidrug resistant, and infections are notoriously difficult to treat. The World Health Organization recently highlighted carbapenem-resistantA. baumanniias a “critical priority” for the development of new antimicrobials because of the risk to human health posed by this organism. Therefore, it is important to discover the mechanisms used byA. baumanniito survive stresses encountered during infection in order to identify new drug targets. In this study, by use ofin vivoimaging, we identified hydrogen peroxide (H2O2) as a stressor produced in the lung duringA. baumanniiinfection and defined OxyR as a transcriptional regulator of the H2O2stress response. Upon exposure to H2O2,A. baumanniidifferentially transcribes several hundred genes. However, the transcriptional upregulation of genes predicted to detoxify hydrogen peroxide is abolished in anA. baumanniistrain in which the transcriptional regulatoroxyRis genetically inactivated. Moreover, inactivation ofoxyRin both antimicrobial-susceptible and multidrug-resistantA. baumanniistrains impairs growth in the presence of H2O2. OxyR is a direct regulator ofkatEandahpF1, which encode the major H2O2-degrading enzymes inA. baumannii, as confirmed through measurement of promoter binding by recombinant OxyR in electromobility shift assays. Finally, anoxyRmutant is less fit than wild-typeA. baumanniiduring infection of the murine lung. This work reveals a mechanism used by this important human pathogen to survive H2O2stress encountered during infection.

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Section: Discussionmentioning

confidence: 91%

Acinetobacter baumanniiOxyR Regulates the Transcriptional Response to Hydrogen Peroxide

et al. 2019

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“…Loss of Trx1 impairs repressing activity of OxyR. In S. oneidensis, the adaptive response to H 2 O 2 -induced oxidative stress is mainly mediated by OxyR, which directly controls transcription of only 5 operons (18,20). S. oneidensis OxyR, unlike its E. coli counterpart, functions as both an activator and a repressor for katB, which encodes the primary catalase responsible for H 2 O 2 degradation (18).…”

Section: Resultsmentioning

confidence: 99%

“…To test this, we set out to determine expression of the katB gene in relevant strains with integrative lacZ reporters used before (19,20). Under normal conditions, expression of katB increased modestly in the trxA mutant, ϳ1.9-fold higher than that in the wild type ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Intriguingly, both OxyR and OhrR display novel features. Unlike most OxyRs studied to date that function as an activator only (with respect to genes for ROS protection systems), S. oneidensis OxyR can both activate and repress expression of some of its target genes (18,20,21). Additionally, the OxyR regulon is substantially contracted, to probably only five members, whereas OhrR controls SO_1563 (encoding putative cytoplasmic GSH peroxidase) in addition to ohrA.…”

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confidence: 99%

“…Members of the genus Shewanella, a group of facultative Gram-negative anaerobes, are renowned for their versatile respiratory abilities and thrive in redox-stratified environments prone to ROS generation (17). In Shewanella oneidensis, the genus representative in which oxidative stress response has been intensively studied, OxyR and OhrR are primary transcriptional regulators mediating the cellular responses to H 2 O 2 and OPs, respectively (18)(19)(20). Intriguingly, both OxyR and OhrR display novel features.…”

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confidence: 99%

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Distinct Roles of Shewanella oneidensis Thioredoxin in Regulation of Cellular Responses to Hydrogen and Organic Peroxides

Xue

Sun

Kong

et al. 2019

Appl Environ Microbiol

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The thioredoxin (Trx) and glutaredoxin (Grx) antioxidant systems are deeply involved in bacterial response to oxidative stress, but to date, we know surprisingly little about the roles of these systems in response to reactive oxygen species (ROS) other than hydrogen peroxide (H2O2). In this study, we used Shewanella oneidensis, an environmental bacterium, as a research model to investigate the roles of Trx and Grx in oxidative stress response because it has functionally intertwined ROS responsive regulators OxyR and OhrR. We found that Trx1 is the major thiol/disulfide redox system and that in its absence a Grx system becomes essential under normal conditions. Although overshadowed by Trx1 in the wild type, Trx2 can fully replace Trx1 in physiology when overproduced. Trx1 is required for OxyR to function as a repressor but, more importantly, plays a critical role in the cellular response to organic peroxide (OP) by mediating the redox status of OhrR but not OP scavenger OhrA. While none of the trx and grx genes are OxyR dependent, trxA and trxC are affected by OhrR indirectly. Additional data suggest that depletion of glutathione is likely the cue to trigger induced expression of trxA and trxC. These findings underscore the particular importance of Trx in the bacterial OP stress response. IMPORTANCE The Trx and Grx systems are deeply involved in bacterial responses to H2O2-induced oxidative stress. However, little is known about their roles in response to other ROS, such as organic peroxides (OPs). In this study, we used S. oneidensis as a research model to investigate the interplay between Trx/Grx and OxyR/OhrR. We show that Trxs mediate the redox status of transcriptional OP-responding regulator OhrR. Although none of the trx or grx genes are directly controlled by OxyR or OhrR, expression of trxA and trxC is induced by tert-butyl hydroperoxide (t-BHP). We further show that the trxA and trxC genes respond to effects of glutathione (GSH) depletion rather than oxidation. These findings underscore the particular importance of Trx in the bacterial OP stress response.

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Heme homeostasis and its regulation by hemoproteins in bacteria

Li,

Han,

Gao

2024

mLife

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Heme is an important cofactor and a regulatory molecule involved in various physiological processes in virtually all living cellular organisms, and it can also serve as the primary iron source for many bacteria, particularly pathogens. However, excess heme is cytotoxic to cells. In order to meet physiological needs while preventing deleterious effects, bacteria have evolved sophisticated cellular mechanisms to maintain heme homeostasis. Recent advances in technologies have shaped our understanding of the molecular mechanisms that govern the biological processes crucial to heme homeostasis, including synthesis, acquisition, utilization, degradation, trafficking, and efflux, as well as their regulation. Central to these mechanisms is the regulation of the heme, by the heme, and for the heme. In this review, we present state‐of‐the‐art findings covering the biochemical, physiological, and structural characterization of important, newly identified hemoproteins/systems involved in heme homeostasis.

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Defining the binding determinants of Shewanella oneidensis OxyR: Implications for the link between the contracted OxyR regulon and adaptation

Abstract: It is well established that OxyR functions as a transcriptional activator of the peroxide stress response in bacteria, primarily based on studies on Escherichia coli.

Cited by 23 publications

References 45 publications

Acinetobacter baumanniiOxyR Regulates the Transcriptional Response to Hydrogen Peroxide

Acinetobacter baumanniiOxyR Regulates the Transcriptional Response to Hydrogen Peroxide

Distinct Roles of Shewanella oneidensis Thioredoxin in Regulation of Cellular Responses to Hydrogen and Organic Peroxides

Heme homeostasis and its regulation by hemoproteins in bacteria

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