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

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.

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

Antioxidants ◽

10.3390/antiox7100128 ◽

2018 ◽

Vol 7 (10) ◽

pp. 128 ◽

Cited By ~ 14

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.

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Methionine Sulfoxide Reductases Contribute to Anaerobic Fermentative Metabolism in Bacillus cereus

Antioxidants ◽

10.3390/antiox10050819 ◽

2021 ◽

Vol 10 (5) ◽

pp. 819

Author(s):

Catherine Duport ◽

Jean-Paul Madeira ◽

Mahsa Farjad ◽

Béatrice Alpha-Bazin ◽

Jean Armengaud

Keyword(s):

Bacillus Cereus ◽

Oxidant Stress ◽

Physiological Role ◽

Methionine Sulfoxide ◽

Wild Type ◽

Fermentative Metabolism ◽

Methionine Sulfoxide Reductases ◽

Mutant Strains ◽

Oxidation Of Methionine

Reversible oxidation of methionine to methionine sulfoxide (Met(O)) is a common posttranslational modification occurring on proteins in all organisms under oxic conditions. Protein-bound Met(O) is reduced by methionine sulfoxide reductases, which thus play a significant antioxidant role. The facultative anaerobe Bacillus cereus produces two methionine sulfoxide reductases: MsrA and MsrAB. MsrAB has been shown to play a crucial physiological role under oxic conditions, but little is known about the role of MsrA. Here, we examined the antioxidant role of both MsrAB and MrsA under fermentative anoxic conditions, which are generally reported to elicit little endogenous oxidant stress. We created single- and double-mutant Δmsr strains. Compared to the wild-type and ΔmsrAB mutant, single- (ΔmsrA) and double- (ΔmsrAΔmsrAB) mutants accumulated higher levels of Met(O) proteins, and their cellular and extracellular Met(O) proteomes were altered. The growth capacity and motility of mutant strains was limited, and their energy metabolism was altered. MsrA therefore appears to play a major physiological role compared to MsrAB, placing methionine sulfoxides at the center of the B. cereus antioxidant system under anoxic fermentative conditions.

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ROLE OF THIOREDOXINS AND METHIONINE SULFOXIDE REDUCTASES IN THE PATHOPHYSIOLOGY OF PNEUMOCOCCAL MENINGITIS

10.26226/morressier.5731f0d4d462b8029238027a ◽

2016 ◽

Author(s):

Sandra Ribes

Keyword(s):

Pneumococcal Meningitis ◽

Methionine Sulfoxide ◽

Methionine Sulfoxide Reductases

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Role of rgsA in Oxidative Stress Resistance in Pseudomonas aeruginosa

Current Microbiology ◽

10.1007/s00284-021-02580-z ◽

2021 ◽

Author(s):

Shuyi Hou ◽

Jiaqin Zhang ◽

Xiaobo Ma ◽

Qiang Hong ◽

Lili Fang ◽

...

Keyword(s):

Oxidative Stress ◽

Pseudomonas Aeruginosa ◽

Stress Resistance ◽

Oxidative Stress Resistance

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

Cells ◽

10.3390/cells10030645 ◽

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.

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Physiological role of Addicsin-Arl6ip1 complex in oxidative stress control

Proceedings for Annual Meeting of The Japanese Pharmacological Society ◽

10.1254/jpssuppl.93.0_2-p-248 ◽

2020 ◽

Vol 93 (0) ◽

pp. 2-P-248

Author(s):

Misushi J Ikemoto

Keyword(s):

Oxidative Stress ◽

Physiological Role ◽

Stress Control

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Role of Mitochondrial Cytochrome P450 2E1 in Healthy and Diseased Liver

Cells ◽

10.3390/cells11020288 ◽

2022 ◽

Vol 11 (2) ◽

pp. 288

Author(s):

Julie Massart ◽

Karima Begriche ◽

Jessica H. Hartman ◽

Bernard Fromenty

Keyword(s):

Oxidative Stress ◽

Cytochrome P450 ◽

Liver Disease ◽

Fatty Liver ◽

Current Knowledge ◽

Physiological Role ◽

Experimental Investigations ◽

Rat Liver Mitochondria ◽

Cytochrome P450 2E1

Cytochrome P450 2E1 (CYP2E1) is pivotal in hepatotoxicity induced by alcohol abuse and different xenobiotics. In this setting, CYP2E1 generates reactive metabolites inducing oxidative stress, mitochondrial dysfunction and cell death. In addition, this enzyme appears to play a role in the progression of obesity-related fatty liver to nonalcoholic steatohepatitis. Indeed, increased CYP2E1 activity in nonalcoholic fatty liver disease (NAFLD) is deemed to induce reactive oxygen species overproduction, which in turn triggers oxidative stress, necroinflammation and fibrosis. In 1997, Avadhani’s group reported for the first time the presence of CYP2E1 in rat liver mitochondria, and subsequent investigations by other groups confirmed that mitochondrial CYP2E1 (mtCYP2E1) could be found in different experimental models. In this review, we first recall the main features of CYP2E1 including its role in the biotransformation of endogenous and exogenous molecules, the regulation of its expression and activity and its involvement in different liver diseases. Then, we present the current knowledge on the physiological role of mtCYP2E1, its contribution to xenobiotic biotransformation as well as the mechanism and regulation of CYP2E1 targeting to mitochondria. Finally, we discuss experimental investigations suggesting that mtCYP2E1 could have a role in alcohol-associated liver disease, xenobiotic-induced hepatotoxicity and NAFLD.

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PmtA Regulates Pyocyanin Expression and Biofilm Formation in Pseudomonas aeruginosa

Frontiers in Microbiology ◽

10.3389/fmicb.2021.789765 ◽

2021 ◽

Vol 12 ◽

Author(s):

Amy V. Thees ◽

Kathryn M. Pietrosimone ◽

Clare K. Melchiorre ◽

Jeremiah N. Marden ◽

Joerg Graf ◽

...

Keyword(s):

Oxidative Stress ◽

Pseudomonas Aeruginosa ◽

Metal Binding ◽

Biofilm Formation ◽

Binding Capacity ◽

Opportunistic Pathogen ◽

Small Molecular Weight ◽

Heavy Metal Binding ◽

The Impact

The opportunistic pathogen Pseudomonas aeruginosa expresses a small molecular weight, cysteine-rich protein (PmtA), identified as a metallothionein (MT) protein family member. The MT family proteins have been well-characterized in eukaryotes as essential for zinc and copper homeostasis, protection against oxidative stress, and the ability to modify a variety of immune activities. Bacterial MTs share sequence homology, antioxidant chemistry, and heavy metal-binding capacity with eukaryotic MTs, however, the impact of bacterial MTs on virulence and infection have not been well-studied. In the present study, we investigated the role of PmtA in P. aeruginosa PAO1 using a PmtA-deficient strain (ΔpmtA). Here we demonstrated the virulence factor, pyocyanin, relies on the expression of PmtA. We showed that PmtA may be protective against oxidative stress, as an alternative antioxidant, glutathione, can rescue pyocyanin expression. Furthermore, the expression of phzM, which encodes a pyocyanin precursor enzyme, was decreased in the ΔpmtA mutant during early stationary phase. Upregulated pmtA expression was previously detected in confluent biofilms, which are essential for chronic infection, and we observed that the ΔpmtA mutant was disrupted for biofilm formation. As biofilms also modulate antibiotic susceptibility, we examined the ΔpmtA mutant susceptibility to antibiotics and found that the ΔpmtA mutant is more susceptible to cefepime and ciprofloxacin than the wild-type strain. Finally, we observed that the deletion of pmtA results in decreased virulence in a waxworm model. Taken together, our results support the conclusion that PmtA is necessary for the full virulence of P. aeruginosa and may represent a potential target for therapeutic intervention.

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