scholarly journals The Role of Methionine Sulfoxide Reductases in Oxidative Stress Tolerance and Virulence of Staphylococcus aureus and Other Bacteria

Antioxidants ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 128 ◽  
Author(s):  
Vineet Singh ◽  
Kuldeep Singh ◽  
Kyle Baum
Keyword(s):  
Oxidative Stress ◽  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Regulatory Network ◽  
Current Knowledge ◽  
Methionine Sulfoxide ◽  
Oxidative Stress Tolerance ◽  
Methionine Sulfoxide Reductases ◽  
Encoding Genes

Methionine sulfoxide reductases (MSRA1 and MSRB) are proteins overproduced in Staphylococcus aureus during exposure with cell wall-active antibiotics. Later studies identified the presence of two additional MSRA proteins (MSRA2 and MSRA3) in S. aureus. These MSR proteins have been characterized in many other bacteria as well. This review provides the current knowledge about the conditions and regulatory network that mimic the expression of these MSR encoding genes and their role in defense from oxidative stress and virulence.

scholarly journals Methionine Sulfoxide Reductases Protect against Oxidative Stress in Staphylococcus aureus Encountering Exogenous Oxidants and Human Neutrophils

2013 ◽  
Vol 6 (3) ◽  
pp. 353-364 ◽  
Author(s):  
Yun Yun Pang ◽  
Jamie Schwartz ◽  
Sarah Bloomberg ◽  
Jeffrey M. Boyd ◽  
Alexander R. Horswill ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Staphylococcus Aureus ◽  
Methionine Sulfoxide ◽  
Human Neutrophils ◽  
Methionine Sulfoxide Reductases

scholarly journals Role of Methionine Sulfoxide Reductases A and B of Enterococcus faecalis in Oxidative Stress and Virulence

2010 ◽  
Vol 78 (9) ◽  
pp. 3889-3897 ◽  
Author(s):  
Chen Zhao ◽  
Axel Hartke ◽  
Marilena La Sorda ◽  
Brunella Posteraro ◽  
Jean-Marie Laplace ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Enterococcus Faecalis ◽  
Galleria Mellonella ◽  
Methionine Sulfoxide ◽  
Peritoneal Macrophages ◽  
Infection Model ◽  
Repair Enzymes ◽  
Methionine Sulfoxide Reductases ◽  
Mouse Peritoneal Macrophages

ABSTRACT Methionine sulfoxide reductases A and B are antioxidant repair enzymes that reduce the S- and R-diastereomers of methionine sulfoxides back to methionine, respectively. Enterococcus faecalis, an important nosocomial pathogen, has one msrA gene and one msrB gene situated in different parts of the chromosome. Promoters have been mapped and mutants have been constructed in two E. faecalis strains (strains JH2-2 and V583) and characterized. For both backgrounds, the mutants are more sensitive than the wild-type parents to exposure to H2O2, and in combination the mutations seem to be additive. The virulence of the mutants has been analyzed in four different models. Survival of the mutants inside mouse peritoneal macrophages stimulated with recombinant gamma interferon plus lipopolysaccharide but not in naïve phagocytes is significantly affected. The msrA mutant is attenuated in the Galleria mellonella insect model. Deficiency in either Msr enzyme reduced the level of virulence in a systemic and urinary tract infection model. Virulence was reconstituted in the complemented strains. The combined results show that Msr repair enzymes are important for the oxidative stress response, macrophage survival, and persistent infection with E. faecalis.

scholarly journals Gene Expression and Physiological Role of Pseudomonas aeruginosa Methionine Sulfoxide Reductases during Oxidative Stress

2013 ◽  
Vol 195 (15) ◽  
pp. 3299-3308 ◽  
Author(s):  
A. Romsang ◽  
S. Atichartpongkul ◽  
W. Trinachartvanit ◽  
P. Vattanaviboon ◽  
S. Mongkolsuk
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Physiological Role ◽  
Methionine Sulfoxide ◽  
Methionine Sulfoxide Reductases

scholarly journals Regulation of Expression of Oxacillin-Inducible Methionine Sulfoxide Reductases inStaphylococcus aureus

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Kyle R. Baum ◽  
Zulfiqar Ahmad ◽  
Vineet K. Singh
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Methionine Sulfoxide ◽  
Galactosidase Activity ◽  
Growth Phases ◽  
Wild Type ◽  
Regulation Of Expression ◽  
Methionine Sulfoxide Reductases ◽  
Reporter Strains ◽  
Dna Fragment

Cell wall-active antibiotics cause induction of a locus that leads to elevated synthesis of two methionine sulfoxide reductases (MsrA1 and MsrB) inStaphylococcus aureus. To understand the regulation of this locus, reporter strains were constructed by integrating a DNA fragment consisting of themsrA1/msrBpromoter in front of a promoterlesslacZgene in the chromosome of wild-type and MsrA1-, MsrB-, MsrA1/MsrB-, and SigB-deficient methicillin-sensitiveS. aureusstrain SH1000 and methicillin-resistantS. aureusstrain COL. These reporter strains were cultured in TSB and the cellular levels ofβ-galactosidase activity in these cultures were assayed during different growth phases.β-galactosidase activity assays demonstrated that the lack of MsrA1, MsrB, and SigB upregulated themsrA1/msrBpromoter inS. aureusstrain SH1000. InS. aureusstrain COL, the highest level ofβ-galactosidase activity was observed under the conditions when both MsrA1 and MsrB proteins were absent. The data suggest that themsrA1/msrBlocus, in part, is negatively regulated by MsrA1, MsrB, and SigB inS. aureus.

scholarly journals Molecular Mechanisms of Obesity-Linked Cardiac Dysfunction: An Up-Date on Current Knowledge

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 629
Author(s):  
Jorge Gutiérrez-Cuevas ◽  
Ana Sandoval-Rodriguez ◽  
Alejandra Meza-Rios ◽  
Hugo Christian Monroy-Ramírez ◽  
Marina Galicia-Moreno ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Dysfunction ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Peroxisome Proliferator ◽  
White Adipocyte ◽  
Peroxisome Proliferator Activated Receptors ◽  
And Oxidative Stress

Obesity is defined as excessive body fat accumulation, and worldwide obesity has nearly tripled since 1975. Excess of free fatty acids (FFAs) and triglycerides in obese individuals promote ectopic lipid accumulation in the liver, skeletal muscle tissue, and heart, among others, inducing insulin resistance, hypertension, metabolic syndrome, type 2 diabetes (T2D), atherosclerosis, and cardiovascular disease (CVD). These diseases are promoted by visceral white adipocyte tissue (WAT) dysfunction through an increase in pro-inflammatory adipokines, oxidative stress, activation of the renin-angiotensin-aldosterone system (RAAS), and adverse changes in the gut microbiome. In the heart, obesity and T2D induce changes in substrate utilization, tissue metabolism, oxidative stress, and inflammation, leading to myocardial fibrosis and ultimately cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of carbohydrate and lipid metabolism, also improve insulin sensitivity, triglyceride levels, inflammation, and oxidative stress. The purpose of this review is to provide an update on the molecular mechanisms involved in obesity-linked CVD pathophysiology, considering pro-inflammatory cytokines, adipokines, and hormones, as well as the role of oxidative stress, inflammation, and PPARs. In addition, cell lines and animal models, biomarkers, gut microbiota dysbiosis, epigenetic modifications, and current therapeutic treatments in CVD associated with obesity are outlined in this paper.

scholarly journals The Phosphoarginine Phosphatase PtpB from Staphylococcus aureus Is Involved in Bacterial Stress Adaptation during Infection

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 645
Author(s):  
Mohamed Ibrahem Elhawy ◽  
Sylvaine Huc-Brandt ◽  
Linda Pätzold ◽  
Laila Gannoun-Zaki ◽  
Ahmed Mohamed Mostafa Abdrabou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Staphylococcus Aureus ◽  
Treatment Strategies ◽  
Physiological Role ◽  
Aureus Strain ◽  
Stress Adaptation ◽  
Cellular Mechanisms ◽  
Host Interaction ◽  
Liver And Kidney

Staphylococcus aureus continues to be a public health threat, especially in hospital settings. Studies aimed at deciphering the molecular and cellular mechanisms that underlie pathogenesis, host adaptation, and virulence are required to develop effective treatment strategies. Numerous host-pathogen interactions were found to be dependent on phosphatases-mediated regulation. This study focused on the analysis of the role of the low-molecular weight phosphatase PtpB, in particular, during infection. Deletion of ptpB in S. aureus strain SA564 significantly reduced the capacity of the mutant to withstand intracellular killing by THP-1 macrophages. When injected into normoglycemic C57BL/6 mice, the SA564 ΔptpB mutant displayed markedly reduced bacterial loads in liver and kidney tissues in a murine S. aureus abscess model when compared to the wild type. We also observed that PtpB phosphatase-activity was sensitive to oxidative stress. Our quantitative transcript analyses revealed that PtpB affects the transcription of various genes involved in oxidative stress adaptation and infectivity. Thus, this study disclosed first insights into the physiological role of PtpB during host interaction allowing us to link phosphatase-dependent regulation to oxidative bacterial stress adaptation during infection.

scholarly journals The Role of Oxidative Stress in NAFLD–NASH–HCC Transition—Focus on NADPH Oxidases

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 687
Author(s):  
Daniela Gabbia ◽  
Luana Cannella ◽  
Sara De De Martin
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Current Knowledge ◽  
Mechanisms Of Action ◽  
Nadph Oxidases ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

A peculiar role for oxidative stress in non-alcoholic fatty liver disease (NAFLD) and its transition to the inflammatory complication non-alcoholic steatohepatitis (NASH), as well as in its threatening evolution to hepatocellular carcinoma (HCC), is supported by numerous experimental and clinical studies. NADPH oxidases (NOXs) are enzymes producing reactive oxygen species (ROS), whose abundance in liver cells is closely related to inflammation and immune responses. Here, we reviewed recent findings regarding this topic, focusing on the role of NOXs in the different stages of fatty liver disease and describing the current knowledge about their mechanisms of action. We conclude that, although there is a consensus that NOX-produced ROS are toxic in non-neoplastic conditions due to their role in the inflammatory vicious cycle sustaining the transition of NAFLD to NASH, their effect is controversial in the neoplastic transition towards HCC. In this regard, there are indications of a differential effect of NOX isoforms, since NOX1 and NOX2 play a detrimental role, whereas increased NOX4 expression appears to be correlated with better HCC prognosis in some studies. Further studies are needed to fully unravel the mechanisms of action of NOXs and their relationships with the signaling pathways modulating steatosis and liver cancer development.

scholarly journals Influence of Metal-Resistant Staphylococcus aureus Strain K1 on the Alleviation of Chromium Stress in Wheat

Agronomy ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1354 ◽  
Author(s):  
Fanrong Zeng ◽  
Munazza Zahoor ◽  
Muhammad Waseem ◽  
Alia Anayat ◽  
Muhammad Rizwan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Staphylococcus Aureus ◽  
Anthropogenic Activities ◽  
Toxic Metal ◽  
Triticum Aestivum L ◽  
Aureus Strain ◽  
Peat Moss ◽  
Cr Toxicity ◽  
Living Organisms

Chromium (Cr) is recognized as a toxic metal that has detrimental effects on living organisms; notably, it is discharged into soil by various industries as a result of anthropogenic activities. Microbe-assisted phytoremediation is one of the most emergent and environmentally friendly methods used for the detoxification of pollutants. In this study, the alleviative role of Staphylococcus aureus strain K1 was evaluated in wheat (Triticum aestivum L.) under Cr stress. For this, various Cr concentrations (0, 25, 50 and 100 mg·kg−1) with and without peat-moss-based bacterial inoculum were applied in the soil. Results depicted that Cr stress reduced the plants’ growth by causing oxidative stress in the absence of S. aureus K1 inoculation. However, the application of S. aureus K1 regulated the plants’ growth and antioxidant enzymatic activities by reducing oxidative stress and Cr toxicity through conversion of Cr6+ to Cr3+. The Cr6+ uptake by wheat was significantly reduced in the S. aureus K1 inoculated plants. It can be concluded that the application of S. aureus K1 could be an effective approach to alleviate the Cr toxicity in wheat and probably in other cereals grown under Cr stress.

scholarly journals Staphylococcus aureus peptide methionine sulfoxide reductases protect from human whole blood killing.

2021 ◽  
Author(s):  
William N. Beavers ◽  
Ashley L. DuMont ◽  
Andrew J. Monteith ◽  
K. Nichole Maloney ◽  
Keri A. Tallman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Staphylococcus Aureus ◽  
Protein Oxidation ◽  
Whole Blood ◽  
Methionine Sulfoxide ◽  
Methionine Sulfoxide Reductase ◽  
Human Whole Blood ◽  
Infection Models ◽  
Intraperitoneal Infection ◽  
Peptide Methionine Sulfoxide Reductase

The generation of oxidative stress is a host strategy used to control Staphylococcus aureus infections. Sulfur containing amino acids, cysteine and methionine, are particularly susceptible to oxidation because of the inherent reactivity of sulfur. Due to the constant threat of protein oxidation, many systems evolved to protect S. aureus from protein oxidation or to repair protein oxidation after it occurs. The S. aureus peptide methionine sulfoxide reductase (Msr) system reduces methionine sulfoxide to methionine. Staphylococci have four Msr enzymes, which all perform this reaction. Deleting all four msr genes in USA300 LAC (Δmsr) sensitizes S. aureus to hypochlorous acid (HOCl) killing, however, Δmsr does not exhibit increased sensitivity to H2O2 stress or superoxide anion stress generated by paraquat or pyocyanin. Consistent with increased susceptibility to HOCl killing, Δmsr is slower to recover following co-culture with both murine and human neutrophils than USA300 wildtype. Δmsr is attenuated for dissemination to the spleen following murine intraperitoneal infection and exhibits reduced bacterial burdens in a murine skin infection model. Notably, no differences in bacterial burdens were observed in any organ following murine intravenous infection. Consistent with these observations, USA300 wildtype and Δmsr have similar survival phenotypes when incubated with murine whole blood. However, Δmsr is killed more efficiently by human whole blood. These findings indicate that species-specific immune cell composition of the blood may influence the importance of Msr enzymes during S. aureus infection of the human host. IMPORTANCE Oxidative stress is a host defense strategy to control bacterial infections, and bacteria have evolved systems to counteract this innate immune defense. Here we investigate the peptide methionine sulfoxide reductase system in Staphylococcus aureus that repairs oxidized methionine residues in proteins, preventing the need to resynthesize damaged proteins de novo. Most organisms have an Msr system, and in S. aureus these enzymes are protective against HOCl killing, the major oxidant produced by neutrophils. The S. aureus Msr system does not have a significant contribution to pathogenesis in bacteremia murine infection models but does protect S. aureus in both skin and intraperitoneal infection models. Strains lacking Msr activity are killed equivalently to wildtype by murine whole blood, and Δmsr is more sensitive to killing by human whole blood than the wildtype strain. These data identify the Msr enzymes as important and potentially specific factors for S. aureus pathogenesis in the human host.

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