Group A Streptococcus co-ordinates manganese import and iron efflux in response to hydrogen peroxide stress

Abstract Bacterial pathogens encounter a variety of adverse physiological conditions during infection, including metal starvation, metal overload and oxidative stress. Here, we demonstrate that group A Streptococcus (GAS) utilises Mn(II) import via MtsABC during conditions of hydrogen peroxide stress to optimally metallate the superoxide dismutase, SodA, with Mn. MtsABC expression is controlled by the DtxR family metalloregulator MtsR, which also regulates the expression of Fe uptake systems in GAS. Our results indicate that the SodA in GAS requires Mn for full activity and has lower activity when it contains Fe. As a consequence, under conditions of hydrogen peroxide stress where Fe is elevated, we observed that the PerR-regulated Fe(II) efflux system PmtA was required to reduce intracellular Fe, thus protecting SodA from becoming mismetallated. Our findings demonstrate the co-ordinate action of MtsR-regulated Mn(II) import by MtsABC and PerR-regulated Fe(II) efflux by PmtA to ensure appropriate Mn(II) metallation of SodA for optimal superoxide dismutase function.

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Manganese Homeostasis in Group A Streptococcus Is Critical for Resistance to Oxidative Stress and Virulence

mBio ◽

10.1128/mbio.00278-15 ◽

2015 ◽

Vol 6 (2) ◽

Cited By ~ 34

Author(s):

Andrew G. Turner ◽

Cheryl-lynn Y. Ong ◽

Christine M. Gillen ◽

Mark R. Davies ◽

Nicholas P. West ◽

...

Keyword(s):

Oxidative Stress ◽

Hydrogen Peroxide ◽

Transition Metal ◽

Metal Ion ◽

Double Mutant ◽

Efflux Pump ◽

Group A Streptococcus ◽

Wild Type ◽

Group A

ABSTRACT Streptococcus pyogenes (group A Streptococcus [GAS]) is an obligate human pathogen responsible for a spectrum of human disease states. Metallobiology of human pathogens is revealing the fundamental role of metals in both nutritional immunity leading to pathogen starvation and metal poisoning of pathogens by innate immune cells. Spy0980 (MntE) is a paralog of the GAS zinc efflux pump CzcD. Through use of an isogenic mntE deletion mutant in the GAS serotype M1T1 strain 5448, we have elucidated that MntE is a manganese-specific efflux pump required for GAS virulence. The 5448ΔmntE mutant had significantly lower survival following infection of human neutrophils than did the 5448 wild type and the complemented mutant (5448ΔmntE::mntE). Manganese homeostasis may provide protection against oxidative stress, explaining the observed ex vivo reduction in virulence. In the presence of manganese and hydrogen peroxide, 5448ΔmntE mutant exhibits significantly lower survival than wild-type 5448 and the complemented mutant. We hypothesize that MntE, by maintaining homeostatic control of cytoplasmic manganese, ensures that the peroxide response repressor PerR is optimally poised to respond to hydrogen peroxide stress. Creation of a 5448ΔmntE-ΔperR double mutant rescued the oxidative stress resistance of the double mutant to wild-type levels in the presence of manganese and hydrogen peroxide. This work elucidates the mechanism for manganese toxicity within GAS and the crucial role of manganese homeostasis in maintaining GAS virulence. IMPORTANCE Manganese is traditionally viewed as a beneficial metal ion to bacteria, and it is also established that most bacteria can tolerate high concentrations of this transition metal. In this work, we show that in group A Streptococcus, mutation of the mntE locus, which encodes a transport protein of the cation diffusion facilitator (CDF) family, results in accumulation of manganese and sensitivity to this transition metal ion. The toxicity of manganese is indirect and is the result of a failure of the PerR regulator to respond to oxidative stress in the presence of high intracellular manganese concentrations. These results highlight the importance of MntE in manganese homeostasis and maintenance of an optimal manganese/iron ratio in GAS and the impact of manganese on resistance to oxidative stress and virulence.

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The Group A Streptococcus (GAS) and Oxidative Stress Interaction

BioNanoScience ◽

10.1007/s12668-016-0327-5 ◽

2016 ◽

Vol 7 (1) ◽

pp. 233-236 ◽

Cited By ~ 1

Author(s):

Charles Emene ◽

Irina E. Kravchenko ◽

Maxim V. Zamergrad ◽

Albert A. Rizvanov

Keyword(s):

Oxidative Stress ◽

Group A Streptococcus ◽

Group A ◽

And Oxidative Stress

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Hydrogen peroxide and quercetin induced changes on cell viability, apoptosis and oxidative stress in HepG2 cells

Current Nutraceuticals ◽

10.2174/2665978601999200807160528 ◽

2020 ◽

Vol 01 ◽

Author(s):

Ayşe Mine Yılmaz ◽

Gökhan Biçim ◽

Kübra Toprak ◽

Betül Karademir Yılmaz ◽

Irina Milisav ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Cycle ◽

Hydrogen Peroxide ◽

Cell Viability ◽

Hepg2 Cells ◽

Proteasome Activity ◽

Cell Cycle Phases ◽

Induced Changes ◽

And Oxidative Stress ◽

Quercetin Treatment

Background: Different cellular responses influence the progress of cancer. In this study, we have investigated the effect of hydrogen peroxide and quercetin induced changes on cell viability, apoptosis and oxidative stress in human hepatocellular carcinoma (HepG2) cells. Methods: The effects of hydrogen peroxide and quercetin on cell viability, cell cycle phases and oxidative stress related cellular changes were investigated. Cell viability was assessed by WST-1 assay. Apoptosis rate, cell cycle phase changes and oxidative stress were measured by flow cytometry. Protein expressions of p21, p27, p53, NF-Kβ-p50 and proteasome activity were determined by Western blot and fluorometry, respectively. Results: Hydrogen peroxide and quercetin treatment resulted in decreased cell viability and increased apoptosis in HepG2 cells. Proteasome activity was increased by hydrogen peroxide but decreased by quercetin treatment. Conclusion: Both agents resulted in decreased p53 protein expression and increased cell death by different mechanisms regarding proteostasis and cell cycle phases.

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Simultaneous miRNA and mRNA Transcriptome Profiling of Differentiating Equine Satellite Cells Treated with Gamma-Oryzanol and Exposed to Hydrogen Peroxide

Nutrients ◽

10.3390/nu10121871 ◽

2018 ◽

Vol 10 (12) ◽

pp. 1871

Author(s):

Karolina Chodkowska ◽

Anna Ciecierska ◽

Kinga Majchrzak ◽

Piotr Ostaszewski ◽

Tomasz Sadkowski

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Hydrogen Peroxide ◽

Cell Viability ◽

Satellite Cells ◽

Cell Damage ◽

Quantitative Polymerase Chain Reaction ◽

Mirna Gene ◽

Gamma Oryzanol ◽

And Oxidative Stress

Gamma-oryzanol (GO) is a popular supplement for performance horses, dogs, and humans. Previous studies indicated that GO supplementation decreases creatine kinase activity and lactate level after exercise and may affect oxidative stress in Thoroughbred horses. GO may change genes expression in equine satellite cells (ESC). The purpose of this study was to evaluate the effect of GO on miRNA, gene expression, oxidative stress, and cell damage and viability in differentiating ESC pretreated with hydrogen peroxide (H2O2). ESCs were obtained from a young horse’s skeletal muscle. ESCs were pre-incubated with GO (24 h) and then exposed to H2O2 for one hour. For the microRNA and gene expression assessment, the microarray technique was used. Identified miRNAs and genes were validated using real time-quantitative polymerase chain reaction. Several tests related to cell viability, cell damage, and oxidative stress were performed. The microarray analysis revealed differences in 17 miRNAs and 202 genes between GO-treated and control ESC. The tests related to apoptosis, cell viability, and oxidative stress showed that GO affects these processes to varying degrees. Our results suggest that GO can change miRNA and gene expression and may impact the processes involved in tissue repairing after an injury.

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Redox Status in Women with Rheumathoid Arthritis

Serbian Journal of Experimental and Clinical Research ◽

10.2478/sjecr-2018-0047 ◽

2018 ◽

Vol 0 (0) ◽

Cited By ~ 1

Author(s):

Aleksandra Vranic ◽

Aleksandra Antovic ◽

Nevena Draginic ◽

Marijana Andjic ◽

Marko Ravic ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Oxidative Stress ◽

Hydrogen Peroxide ◽

Lipid Peroxidation ◽

Superoxide Dismutase ◽

Cartilage Damage ◽

Thiobarbituric Acid ◽

Antioxidant Defense System ◽

Redox Status ◽

Female Population

Abstract The aim of this study was to assess oxidative status and to set baseline characteristics for female population with established rheumatoid arthritis. Total of 42 patients with rheumatoid arthritis and 48 age- and sex-matched controls were included in the study. Clinical examination was performed and assessed disease activity. Peripheral blood samples were used for all the assays. The markers of oxidative stress were assessed, including plasma levels of index of lipid peroxidation - thiobarbituric acid reactive substances, hydrogen peroxide, superoxide anion radical, nitrites and activity of superoxide dismutase, catalase and reduced glutathione levels as antioxidant parameters. In the patients group, levels of hydrogen peroxide and index of lipid peroxidation were higher than in controls. Patients with rheumatoid arthritis had decreased superoxide dismutase and catalase activity compared to healthy subjects. Interestingly, controls had higher levels of nitrites compared to patients. Patients showed a marked increase in reactive oxygen species formation and lipid peroxidation as well as decrease in the activity of antioxidant defense system leading to oxidative stress which may contribute to tissue and cartilage damage and hence to the chronicity of the disease.

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Aging and oxidative stress alter DNA repair mechanisms in male germ cells of superoxide dismutase-1 null mice

Biology of Reproduction ◽

10.1093/biolre/ioab114 ◽

2021 ◽

Author(s):

Paulina Nguyen-Powanda ◽

Bernard Robaire

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Dna Repair ◽

Superoxide Dismutase ◽

Germ Cells ◽

Superoxide Dismutase 1 ◽

Male Germ Cells ◽

Dna Repair Mechanisms ◽

Repair Mechanisms ◽

And Oxidative Stress

Abstract The efficiency of antioxidant defense system decreases with aging, thus resulting in high levels of reactive oxygen species (ROS) and DNA damage in spermatozoa. This damage can lead to genetic disorders in the offspring. There are limited studies investigating the effects of the total loss of antioxidants, such as superoxide dismutase-1 (SOD1), in male germ cells as they progress through spermatogenesis. In this study, we evaluated the effects of aging and removing SOD1 (in male germ cells of SOD1-null (Sod1−/−) mice) in order to determine the potential mechanism(s) of DNA damage in these cells. Immunohistochemical analysis showed an increase in lipid peroxidation and DNA damage in the germ cells of aged wild-type (WT) and Sod1−/− mice of all age. Immunostaining of OGG1, a marker of base excision repair (BER), increased in aged WT and young Sod1−/− mice. In contrast, immunostaining intensity of LIGIV and RAD51, markers of non-homologous end-joining (NHEJ) and homologous recombination (HR), respectively, decreased in aged and Sod1−/− mice. Gene expression analysis showed similar results with altered mRNA expression of these key DNA repair transcripts in pachytene spermatocytes and round spermatids of aged and Sod1−/− mice. Our study indicates that DNA repair pathway markers of BER, NHEJ, and HR are differentially regulated as a function of aging and oxidative stress in spermatocytes and spermatids, and aging enhances the repair response to increased oxidative DNA damage, whereas impairments in other DNA repair mechanisms may contribute to the increase in DNA damage caused by aging and the loss of SOD1.

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