Revisiting oxygen toxicity: evolution and adaptation to superoxide in a SOD-deficient bacterial pathogen [paraquat]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1167677 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Defenses against oxidants are crucial for the virulence of pathogens, with superoxide scavenging enzymes (SOSEs) playing a vital role for most aerobes. However, our knowledge of superoxide adaptation primarily stems from the study of SOSE-encoding bacteria. Here, we investigated the evolution of a naturally SOSE-deficient pathogen (Leptospira spp.), along with the alternative mechanisms it recruits to combat superoxide stress. We demonstrate that emergence of pathogenic Leptospira correlated with SOD loss, but that a long-lasting adaptation to superoxide remains possible. We reveal that cysteine and leucine biosynthesis are the most induced pathways in response to superoxide and demonstrate the importance of sulfur metabolism in superoxide adaptation in this SOSE-deficient model. We also propose cysteine oxidation as a key mediator of superoxide toxicity in the absence of SOSEs. This study challenges our conventional understanding of the oxygen toxicity theory and proposes a new model of superoxide adaptation through metabolic rewiring in bacteria.
2025-07-15 | GSE278514 | GEO
Project description:Defenses against oxidants are crucial for the virulence of pathogens, with superoxide scavenging enzymes (SOSEs) playing a vital role for most aerobes. However, our knowledge of superoxide adaptation primarily stems from the study of SOSE-encoding bacteria. Here, we investigated the evolution of a naturally SOSE-deficient pathogen (Leptospira spp.), along with the alternative mechanisms it recruits to combat superoxide stress. We demonstrate that emergence of pathogenic Leptospira correlated with SOD loss, but that a long-lasting adaptation to superoxide remains possible. We reveal that cysteine and leucine biosynthesis are the most induced pathways in response to superoxide and demonstrate the importance of sulfur metabolism in superoxide adaptation in this SOSE-deficient model. We also propose cysteine oxidation as a key mediator of superoxide toxicity in the absence of SOSEs. This study challenges our conventional understanding of the oxygen toxicity theory and proposes a new model of superoxide adaptation through metabolic rewiring in bacteria.
2025-07-15 | GSE278513 | GEO
Project description:Revisiting oxygen toxicity: evolution and adaptation to superoxide in a SOD-deficient bacterial pathogen
| PRJNA1167678 | ENA
Project description:To explore the molecular mechanisms of lifespan extension in sod-2 mutants in an unbiased manner, we used RNA sequencing to identify differentially expressed genes in sod-2 mutants compared to wild-type worms. We found a large number of gene expression changes at day 1 of adulthood and much fewer at day 8. Upregulated genes in sod-2 mutants included genes involved in innate immunity and cuticle development. There were many more differentially expressed genes between day 1 and day 8 of adulthood compared to differences between the genotypes.
2025-02-25 | GSE286219 | GEO
Project description:Molecular mechanisms of lifespan extension in long-lived mitocondrial superoxide dismutase sod-2 mutants
| PRJNA1208437 | ENA
Project description:Exposure to Paraquat and RNA interference knockdown of mitochondrial superoxide dismutase (Sod2) are known to result in significant lifespan reduction, locomotor dysfunction, and mitochondrial degeneration in Drosophila melanogaster. Both perturbations increase the flux of superoxide, a progenitor reactive oxygen species, but the molecular underpinnings of the resulting phenotypes are poorly understood. Improved understanding of such processes could lead to advances in the treatment of numerous age-related disorders. Superoxide toxicity can act through protein carbonylation. Analysis of carbonylated proteins is attractive since reactive carbonyl groups are not present in the twenty canonical amino acids and are amenable to labeling and enrichment strategies. Here, carbonylated proteins were labeled with biotin hydrazide and enriched on streptavidin-coated beads. On-bead digestion was used to release carbonylated protein peptides, with relative abundance ratios versus controls obtained using the iTRAQ mass spectrometry-based proteomics approach. While Paraquat exposure and Sod2 knockdown have similar phenotypes, differences in protein carbonylation were anticipated because Paraquat exposure was expected to increase the concentration of superoxide throughout the cell while Sod2 knockdown was only expected to raise the concentration of superoxide in the mitochondrial matrix. Paraquat exposure resulted in widespread increases in carbonylated protein relative abundance: the median Paraquat-exposed to control carbonylated protein relative abundance ratio was 1.53. For Sod2 knockdown, in contrast, the median carbonylated protein relative abundance ratios were 1.13 versus the RNA interference driver control and 1.05 versus the RNA interference transgene control. However, some proteins did show large increases in carbonylated protein relative abundance on Sod2 knockdown, most notably cytochrome c oxidase subunit Vb, possibly providing some indication of the molecular basis of the Sod2-knockdown phenotype.
2014-11-26 | PXD001528 | Pride
Project description:We used microarrays to detail Arabidopsis gene expression in response to paraquat, a herbicide that acts as a terminal oxidant of photosystem I that in the light leads to the enhanced generation of superoxide and hydrogen peroxide inside plastids. Within a few hours after paraquat treatment changes in nuclear gene expression occur. Distinct sets of genes were activated that were different from those induced by another reactive oxygen species, singlet oxygen. Keywords: Time course
2008-02-11 | GSE10464 | GEO
Project description:Mitochondrial superoxide produced by low concentrations of the pro-oxidant paraquat increases C. elegans lifespan. We found that paraquat acts by intensifying RAS-dependent ROS signaling (RDRS) to alter the expression of >50% of the genome and control animal composition and physiology. We show that RDRS is regulated by negative feedback from SOD-1-dependent conversion of superoxide into cytoplasmic hydrogen peroxide, which in turn acts on a redox-sensitive cysteine (C118) of the RAS homologue LET-60ras. Preventing C118 oxidation by replacement with serine, or mimicking oxidation by replacement with aspartic acid, leads to opposite changes in the expression of thousands of genes. We show that paraquat acts through RDRS to exacerbate and accelerate gene expression changes that are normally observed at the end of post-embryonic development. The identities of the genes affected by paraquat suggest that RDRS stimulation extends lifespan by increasing turnover and repair while moderating damage from metabolic activity.
2022-12-07 | GSE200912 | GEO
Project description:A known human SNP in the matrix-binding domain of extracellular superoxide dismutase (EC-SOD), with an arginine to glycine substitution at position 213 (R213G), redistributes EC-SOD from the matrix into extracellular fluids. We reported that, following bleomycin (bleo), knock-in mice harboring the human R213G SNP (R213G mice), compared to wild-type (WT) littermates exhibit enhanced resolution of inflammation and protection against fibrosis. We tested the hypothesis that the EC-SOD R213G SNP promotes resolution via accelerated apoptosis of recruited alveolar macrophage (recAM).
2022-02-01 | GSE127345 | GEO
Project description:SoxR and SoxS constitute an intracellular signal response system that rapidly detects changes in superoxide levels and modulates gene expression in E. coli. A time series microarray design was used to identify co-regulated SoxRS dependent and independent genes affected by superoxide Experiment Overall Design: To determine the immediate transcriptional response of E. coli to superoxide, we conducted a time series assay of mRNA levels immediately following the addition of paraquat. The wild type strain MG1655 and a strain with a precise deletion in soxR was grown in EZ Rich Defined Medium, a modification of Neidhardtâs defined rich medium. When cultures reached an OD600=0.5, 250µM paraquat (PQ) was added, a concentration that triggers the SoxRS transcriptional cascade, but only has a small effect on exponential growth rate in rich media. Samples were taken immediately before exposure to PQ, and every 2 minutes after exposure, for 10 minutes.
2008-06-15 | E-GEOD-6992 | biostudies-arrayexpress