The fused methionine sulfoxide reductase MsrAB promotes oxidative stress defense and bacterial virulence in Fusobacterium nucleatum
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA729437 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14509073_1.fastq.gz | Fastqsanger.gz | |||
| SRR14509073_2.fastq.gz | Fastqsanger.gz | |||
| SRR14509074_1.fastq.gz | Fastqsanger.gz | |||
| SRR14509074_2.fastq.gz | Fastqsanger.gz | |||
| SRR14509075_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 40 |
Similar Datasets
Project description:Recognizably associated with oral infections, adverse pregnancy outcomes, and colorectal cancer, the Gram-negative oral bacterium Fusobacterium nucleatum is known to colonize many extraoral sites including placenta and colon. How this anaerobe copes with oxidative stress imposed by the host immune response in various tissues is unknown. Here, we revealed that F. nucleatum harbors a gene locus coding for a single, fused methionine sulfoxide reductase (MsrAB), a two-component transduction system (ModRS), thioredoxin (Trx)- and cytochrome c (CcdA)-like proteins. Considering their role in oxidative stress responses, we demonstrated that these genes were increasingly expressed when fusobacterial cells were exposed to hydrogen peroxide. Comparative transcriptome analysis of the parental and modR mutant strains revealed that the response regulator ModR regulates a large regulon including trx, ccdA, and many metabolic genes. Significantly, mutants lacking individual genes within the msrAB locus, including msrAB, were sensitive to reactive oxygen species and defective in adherence/invasion of colorectal epithelial cells, as compared to the parental strain. The msrAB mutant was also defective in survival in macrophage, unlike the rescued and parental strains. Strikingly, in an experimental model of preterm birth this mutant was severely attenuated in virulence, for it failed to colonize the placenta and spread to the amniotic fluid. The results support that the MsrAB system represents a major pathway that protects fusobacteria against oxidative damage and confers virulence and that MsrAB-mediated oxidative stress defense is subjected to regulation by the two-component transduction system ModRS.
2022-03-28 | GSE174320 | GEO
Project description:Methionine sulfoxide reductase A (MsrA) is an antioxidant repair enzyme that reduces the oxidized methionine (Met-O) in proteins to methionine (Met). It plays a pivotal role in the cellular processes has been well established by overexpressing, silencing and knocking down of MsrA or by deleting the gene encoding MsrA in several species. We are specifically interested in understanding the role of secreted MsrA of bacterial pathogens. To elucidate this, we infected mouse bone marrow derived macrophages (BMDMs) with recombinant Mycobacterium smegmatis strain (MSM) secreting a bacterial MsrA or M. smegmatis strain (MSC) carrying only the control vector. BMDMs infected with MSM induced higher levels of ROS and TNF-α than BMDMs infected with MSC. The increased ROS and TNF-α in BMDMs infected with MSM correlated with elevated necrotic cell death. Further, RNA-Seq transcriptome analysis of BMDMs infected with MSC and MSM revealed differential expression of protein and RNA coding genes, suggesting that bacterial delivered MsrA could modulate the host cellular processes. Finally, KEGG pathway enrichment analysis identified down-regulation of cancer related signaling genes in MSM infected cells, indicating that MsrA has the potential to regulate the development and progression of cancer.
2023-08-28 | GSE212228 | GEO
Project description:Mycobacterium smegmatis secreting methionine sulfoxide reductase A (MsrA) modulates cellular processes in mouse macrophages
| PRJNA874679 | ENA
Project description:Methionine sulfoxide reductase (Msr) is an important antioxidant enzyme. The mammalian Msr family has four members: MsrA, MsrB1, MsrB2, and MsrB3. We generated a mouse strain with deletion of all four Msr proteins. Deletion was confirmed by Western blotting. The quadruple knockout mouse is viable, and growth, development, and fertility appear normal. However, they are unexpectedly resistanct to oxidative stresses. We therefore determined the RNA expression profile in liver and heart of wild-type and quadruple knockout mice.
2019-10-01 | GSE130394 | GEO
Project description:Fusobacterium nucleatum, an anaerobic Gram-negative bacterium frequently found in the human oral cavity and some extra-oral sites, is implicated in several important diseases: periodontitis, adverse pregnancy outcomes, and colorectal cancer. To date, how this obligate anaerobe copes with oxidative stress and host immunity within multiple human tissues remains unknown. Here, we uncovered a critical role in this process of a multigene locus encoding a single, fused methionine sulfoxide reductase (MsrAB), a two-component signal transduction system (ModRS), and thioredoxin (Trx)- and cytochrome c (CcdA)-like proteins, which are induced when fusobacterial cells are exposed to hydrogen peroxide. Comparative transcriptome analysis revealed that the response regulator ModR regulates a large regulon that includes trx, ccdA, and many metabolic genes. Significantly, specific mutants of the msrAB locus, including msrAB, are sensitive to reactive oxygen species and defective in adherence/invasion of colorectal epithelial cells. Strikingly, the msrAB mutant is also defective in survival in macrophages, and it is severely attenuated in virulence in a mouse model of preterm birth, consistent with its failure to spread to the amniotic fluid and colonize the placenta. Clearly, the MsrAB system regulated by the two-component system ModRS represents a major oxidative stress defense pathway that protects fusobacteria against oxidative damage in immune cells and confers virulence by enabling attachment and invasion of multiple target tissues. IMPORTANCE F. nucleatum colonizes various human tissues, including oral cavity, placenta, and colon. How this obligate anaerobe withstands oxidative stress in host immune cells has not been described. We report here that F. nucleatum possesses a five-gene locus encoding a fused methionine sulfoxide reductase (MsrAB), a two-component signal transduction system (ModRS), and thioredoxin- and cytochrome c-like proteins. Regulated by ModRS, MsrAB is essential for resistance to reactive oxygen species, adherence/invasion of colorectal epithelial cells, and survival in macrophage. Unable to colonize placenta and spread to amniotic fluid, the msrAB mutant failed to induce preterm birth in a murine model.
| S-EPMC9239216 | biostudies-literature
Project description:This project contains the COFRADIC data of two experimental set-ups (swapped labeling) in which methionine sulfoxides were identified in Jurkat cells stressed with hydrogen peroxide. We used a SILAC set-up in which cells were labeled with 12C5 methionine or with 13C5 methionine. One of the set-ups was treated with hydrogen peroxide, the other with H2O. Following lysis proteins were mixed in a 1/1 ratio. We then performed our methionine sulfoxide validation protocol onto the sample identifying methionine sulfoxides in the stressed Jurkat cells.
2011-03-18 | PRD000395 | Pride
Project description:Non-enzymatic oxidative processes in living organisms are one of the inevitable consequences of respiration and environmental conditions. They can lead to the formation of two stereoisomers (R and S) of methionine sulfoxide, and the redox balance between methionine and methionine sulfoxide in proteins has profound functional consequences. Methionine oxidation can be reverted enzymatically by methionine sulfoxide reductases (Msrs). The two enzyme classes known to fulfil this role are MsrA (reducing (S)-sulfoxides), and MsrB (reducing (R)-sulfoxides). They are strictly stereoselective and conserved throughout the tree of life. Under stress conditions such as stationary phase and nutrient starvation, E.coli upregulates expression of MsrA but similar effect has not been described for MsrB, raising a conundrum of the pathway enabling reduction of the (R)-isomer of methionine sulfoxide in these conditions. Using the recently developed chiral fluorescent probes Sulfox-1 we show that in stationary phase stressed E. coli, MsrA does have a stereocomplementary, (R)-sulfoxide-reducing counterpart. However, this activity is not provided by MsrB as expected, but instead by the DMSO reductase complex DmsABC, widely conserved in bacteria. This finding reveals an unexpected diversity in the metabolic enzymes of redox regulation concerning methionine, which should be taken into account in any antibacterial strategies exploiting oxidative stress.
2019-06-12 | PXD013610 | Pride
Project description:Beech trees produce seeds irregularly, necessitating the storage of these seeds for forestation. Despite the acquisition of desiccation tolerance during development, beech seeds lose viability during long-term storage faster than orthodox-type seeds. Seeds stored for short (3 years) and long (20 years) periods under optimal conditions were compared. Aged seeds characterized with germination capacity reduced to 30% displayed increased membrane damage, manifested as electrolyte leakage and lipid peroxidation levels. Analyses have been based on embryonic axes containing higher levels of reactive oxygen species (ROS) and higher levels of protein-bound methionine sulfoxide (MetO) in aged seeds. Using gel-free shotgun proteomics, 3,949 proteins were identified and 2,442 were reliably quantified to indicate 25 proteins with upregulated abundance and 35 with downregulated abundance in beech seeds under long-term storage compared to those under short-term storage. Functional analyses based on gene ontology annotations revealed that nucleic acid binding activity (biological process), hydrolases (molecular function), ribosome organization or biogenesis and transmembrane transport (cellular processes), and ATP synthesis (pathway) were affected in aged seeds. To verify whether MetO the oxidative posttranslational modification of proteins reversed via the action of methionine sulfoxide reductase (Msr) enzymes is involved in ageing of beech seeds we identified 316 and reliably quantified 226 MetO-containing proteins, among which 9 and 19 exhibited significantly up- and downregulated MetO levels, respectively, in beech seeds under long-term storage. Several Msr isoforms were identified and recognized as MsrA1-like, MsrA4, MsrB5 and MsrB5-like in beech seeds. Only MsrA1-like displayed decreased abundance in aged seeds. We demonstrated that the loss of membrane integrity reflected in elevated abundance of membrane proteins had higher impact on seed ageing progress rather than MetO/Msr system.
2024-05-23 | PXD046531 | Pride
Project description:Methionine sulfoxide reductases are present in all aerobic organisms. They contribute to antioxidant defenses by reducing methionine sulfoxide in proteins back to methionine. However, the actual in vivo roles of these reductases are not well defined. Since methionine is an essential amino acid in mammals, we hypothesized that methionine sulfoxide reductases may provide a portion of the dietary methionine requirement by recycling methionine sulfoxide. We used a classical bioassay, the growth of weanling mice fed diets varying in methionine, and applied it to mice genetically engineered to alter the levels of methionine sulfoxide reductase A or B1. Mice of all genotypes were growth retarded when raised on chow containing 0.10% methionine instead of the standard 0.45% methionine. Retardation was significantly greater in knockout mice lacking both reductases. We conclude that the methionine sulfoxide reductases can provide methionine for growth in mice with limited intake of methionine, such as may occur in the wild.
| S-EPMC3358449 | biostudies-literature
Project description:SIGNIFICANCE: Selenium is utilized in the methionine sulfoxide reduction system that occurs in most organisms. Methionine sulfoxide reductases (Msrs), MsrA and MsrB, are the enzymes responsible for this system. Msrs repair oxidatively damaged proteins, protect against oxidative stress, and regulate protein function, and have also been implicated in the aging process. Selenoprotein forms of Msrs containing selenocysteine (Sec) at the catalytic site are found in bacteria, algae, and animals. RECENT ADVANCES: A selenoprotein MsrB1 knockout mouse has been developed. Significant progress in the biochemistry of Msrs has been made, which includes findings of a novel reducing system for Msrs and of an interesting reason for the use of Sec in the Msr system. The effects of mammalian MsrBs, including selenoprotein MsrB1 on fruit fly aging, have been investigated. Furthermore, it is evident that Msrs are involved in methionine metabolism and regulation of the trans-sulfuration pathway. CRITICAL ISSUES: This article presents recent progress in the Msr field while focusing on the physiological roles of mammalian Msrs, functions of selenoprotein forms of Msrs, and their biochemistry. FUTURE DIRECTIONS: A deeper understanding of the roles of Msrs in redox signaling, the aging process, and metabolism will be achieved. The identity of selenoproteome of Msrs will be sought along with characterization of the identified selenoprotein forms. Exploring new cellular targets and new functions of Msrs is also warranted.
| S-EPMC3763222 | biostudies-literature