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 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 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.

scholarly journals Expression of Four Methionine Sulfoxide Reductases inStaphylococcus aureus

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Kuldeep Singh ◽  
Vineet K. Singh
Keyword(s):  
Staphylococcus Aureus ◽  
Stationary Phase ◽  
Expression Pattern ◽  
Growth Phase ◽  
Methionine Sulfoxide ◽  
Phase Growth ◽  
Methionine Sulfoxide Reductases ◽  
Reporter Strains

Staphylococcus aureuspossesses three MsrA enzymes (MsrA1, MsrA2, MsrA3) that reduce the S-epimer of methionine sulfoxide (MetO) and an MsrB enzyme that reduces R-MetO. The fourmsrgenes are expressed from three different promoters. ThemsrA1/msrBgenes are coexpressed. To determine the expression pattern ofmsrgenes, three independent reporter strains were constructed wheremsrpromoter was cloned in front of a promoterlesslacZand the resulting construct was integrated in the chromosome. Using these strains, it was determined that themsrA1/Bexpression is significantly higher inS. aureuscompared tomsrA2ormsrA3. Expression ofmsrA1/Bwas highest during stationary phase growth, but the expression ofmsrA2andmsrA3was highest during the early to midexponential growth phase. Expression ofmsrA1/Bwas induced by oxacillin and the expression ofmsrA3was upregulated by salt. Expression ofmsrA2remained unchanged under all tested conditions.

Multiple methionine sulfoxide reductase genes in Staphylococcus aureus: expression of activity and roles in tolerance of oxidative stress

Microbiology ◽  
2003 ◽  
Vol 149 (10) ◽  
pp. 2739-2747 ◽  
Author(s):  
Vineet K. Singh ◽  
Jackob Moskovitz
Keyword(s):  
Oxidative Stress ◽  
Staphylococcus Aureus ◽  
Stress Response ◽  
Double Mutant ◽  
Mutational Analysis ◽  
Physiological Role ◽  
Methionine Sulfoxide ◽  
Oxidative Stress Response ◽  
Methionine Sulfoxide Reductase ◽  
Activity Data

Staphylococcus aureus contains three genes encoding MsrA-specific methionine sulfoxide reductase (Msr) activity (msrA1, msrA2 and msrA3) and an additional gene that encodes MsrB-specific Msr activity. Data presented here suggest that MsrA1 is the major contributor of the MsrA activity in S. aureus. In mutational analysis, while the total Msr activity in msrA2 mutant was comparable to that of the parent, Msr activity was significantly up-regulated in the msrA1 or msrA1 msrA2 double mutant. Assessment of substrate specificity together with increased reactivity of the cell-free protein extracts of the msrA1 mutants to anti-MsrB polyclonal antibodies in Western analysis provided evidence that increased Msr activity was due to elevated synthesis of MsrB in the MsrA1 mutants. Previously, it was reported that oxacillin treatment of S. aureus cells led to induced synthesis of MsrA1 and a mutation in msrA1 increased the susceptibility of the organism to H2O2. A mutation in the msrA2 gene, however, was not significant for the bacterial oxidative stress response. In complementation assays, while the msrA2 gene was unable to complement the msrA1 msrA2 double mutant for H2O2 resistance, the same gene restored H2O2 tolerance in the double mutant when placed under the control of the msrA1 promoter. However, msrA1 which was able to complement the oxidative stress response in msrA1 mutants could not restore the tolerance of the msrA1 msrA2 mutants to H2O2 when placed under the control of the msrA2 promoter. Additionally, although the oxacillin minimum inhibitory concentration of the msrA1 mutant was comparable to that of the wild-type parent, in shaking liquid culture, the msrA1 mutant responded more efficiently to sublethal doses of oxacillin. The data suggest complex regulation of Msr proteins and a more significant physiological role for msrA1/msrB in S. aureus.

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 Methionine sulfoxide reductase 2 reversibly regulates Mge1, a cochaperone of mitochondrial Hsp70, during oxidative stress

2015 ◽  
Vol 26 (3) ◽  
pp. 406-419 ◽  
Author(s):  
Praveen Kumar Allu ◽  
Adinarayana Marada ◽  
Yerranna Boggula ◽  
Srinivasu Karri ◽  
Thanuja Krishnamoorthy ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Methionine Sulfoxide ◽  
Methionine Sulfoxide Reductase ◽  
Yeast Cells ◽  
Nucleotide Exchange ◽  
New Paradigm ◽  
Methionine Sulfoxide Reductases ◽  
Mitochondrial Hsp70

Peptide methionine sulfoxide reductases are conserved enzymes that reduce oxidized methionines in protein(s). Although these reductases have been implicated in several human diseases, there is a dearth of information on the identity of their physiological substrates. By using Saccharomyces cerevisiae as a model, we show that of the two methionine sulfoxide reductases (MXR1, MXR2), deletion of mitochondrial MXR2 renders yeast cells more sensitive to oxidative stress than the cytosolic MXR1. Our earlier studies showed that Mge1, an evolutionarily conserved nucleotide exchange factor of Hsp70, acts as an oxidative sensor to regulate mitochondrial Hsp70. In the present study, we show that Mxr2 regulates Mge1 by selectively reducing MetO at position 155 and restores the activity of Mge1 both in vitro and in vivo. Mge1 M155L mutant rescues the slow-growth phenotype and aggregation of proteins of mxr2Δ strain during oxidative stress. By identifying the first mitochondrial substrate for Mxrs, we add a new paradigm to the regulation of the oxidative stress response pathway.

scholarly journals The Oxidized Protein Repair Enzymes Methionine Sulfoxide Reductases and Their Roles in Protecting against Oxidative Stress, in Ageing and in Regulating Protein Function

Antioxidants ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 191 ◽  
Author(s):  
Sofia Lourenço dos Santos ◽  
Isabelle Petropoulos ◽  
Bertrand Friguet
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Protein Function ◽  
Methionine Sulfoxide ◽  
Methionine Sulfoxide Reductase ◽  
Methionine Oxidation ◽  
Oxygen Species ◽  
Sulfenic Acid ◽  
Protein Repair ◽  
Methionine Sulfoxide Reductases

Cysteine and methionine residues are the amino acids most sensitive to oxidation by reactive oxygen species. However, in contrast to other amino acids, certain cysteine and methionine oxidation products can be reduced within proteins by dedicated enzymatic repair systems. Oxidation of cysteine first results in either the formation of a disulfide bridge or a sulfenic acid. Sulfenic acid can be converted to disulfide or sulfenamide or further oxidized to sulfinic acid. Disulfide can be easily reversed by different enzymatic systems such as the thioredoxin/thioredoxin reductase and the glutaredoxin/glutathione/glutathione reductase systems. Methionine side chains can also be oxidized by reactive oxygen species. Methionine oxidation, by the addition of an extra oxygen atom, leads to the generation of methionine sulfoxide. Enzymatically catalyzed reduction of methionine sulfoxide is achieved by either methionine sulfoxide reductase A or methionine sulfoxide reductase B, also referred as to the methionine sulfoxide reductases system. This oxidized protein repair system is further described in this review article in terms of its discovery and biologically relevant characteristics, and its important physiological roles in protecting against oxidative stress, in ageing and in regulating protein function.

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