A rubrerythrin locus of Clostridioides difficile encodes enzymes that efficiently detoxify reactive oxygen species

Anaerobe, Journal Year: 2025, Volume and Issue: unknown, P. 102941 - 102941

Published: Jan. 1, 2025

Language: Английский

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Crosstalk Between Antioxidants and Adipogenesis: Mechanistic Pathways and Their Roles in Metabolic Health

Antioxidants, Journal Year: 2025, Volume and Issue: 14(2), P. 203 - 203

Published: Feb. 10, 2025

The interplay between oxidative stress and adipogenesis is a critical factor in the development of obesity its associated metabolic disorders. Excessive reactive oxygen species (ROS) disrupt key transcription factors such as peroxisome proliferator-activated receptor gamma (PPARγ) CCAAT/enhancer-binding protein alpha (C/EBPα), impairing lipid metabolism, promoting adipocyte dysfunction, exacerbating inflammation insulin resistance. Antioxidants, classified endogenous (e.g., glutathione, superoxide dismutase, catalase) exogenous polyphenols, flavonoids, vitamins C E), are pivotal mitigating these effects by restoring redox balance preserving functionality. Endogenous antioxidants neutralize ROS safeguard cellular structures; however, under heightened stress, defenses often insufficient, necessitating dietary supplementation. Exogenous derived from plant-based sources, polyphenols vitamins, act through direct scavenging, upregulation antioxidant enzymes, modulation signaling pathways like nuclear kappa B (NF-κB) PPARγ, reducing peroxidation, inflammation, dysfunction. Furthermore, they influence epigenetic regulation transcriptional networks to restore differentiation limit accumulation. Antioxidant-rich diets, including Mediterranean diet, strongly with improved health, reduced rates, enhanced sensitivity. Advances personalized therapies, guided biomarkers supported novel delivery systems, present promising avenues for optimizing therapeutic interventions. This review, "Crosstalk Between Antioxidants Adipogenesis: Mechanistic Pathways Their Role Metabolic Health", highlights mechanistic which regulate enhance health.

Language: Английский

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Clostridioides difficile superoxide reductase mitigates oxygen sensitivity

Journal of Bacteriology, Journal Year: 2024, Volume and Issue: 206(7)

Published: July 2, 2024

causes a serious diarrheal disease and is common healthcare-associated bacterial pathogen. Although it has major impact on human health, the mechanistic details of

Language: Английский

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Physiological role and complex regulation of O ₂ -reducing enzymes in the obligate anaerobe Clostridioides difficile

mBio, Journal Year: 2024, Volume and Issue: 15(10)

Published: Aug. 27, 2024

, the major cause of antibiotic-associated diarrhea, is a strict anaerobic, sporulating Firmicutes. However, during its infectious cycle, this anaerobe exposed to low oxygen (O

Language: Английский

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Defense arsenal of the strict anaerobe Clostridioides difficile against reactive oxygen species encountered during its infection cycle

mBio, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

ABSTRACT Clostridioides difficile , a strict anaerobe, is the major cause of antibiotic-associated diarrhea. This enteropathogen must adapt to oxidative stress mediated by reactive oxygen species (ROS), notably those released neutrophils and macrophages recruited site infection or endogenously produced upon high (O 2 ) exposure. C. uses superoxide reductase, Sor, several peroxidases detoxify ROS. We showed that Sor has reductase activity in vitro protects bacterium from exposure menadione, donor. After confirming peroxidase rubrerythrin, Rbr, we this enzyme together with peroxiredoxin, Bcp, plays central role detoxification H O promotes survival presence not only but also air 4% . Under concentrations encountered gastrointestinal tract, generated endogenous The two reductases, RevRbr2 FdpF, have participate resistance. CD0828 gene, which contributes protection, forms an operon rbr sor perR encoding -sensing repressor. expression genes ROS reductases protein was induced either air. induction PerR OseR, recently identified -responsive regulator indirectly σ B sigma factor response, whereas bcp controlled IMPORTANCE fundamental intestinal homeostasis, limiting proliferation pathogenic bacteria. important induces intense immune characterized massive recruitment cells responsible for secreting ROS, mainly superoxide. work leads production armada enzymes involved detoxification. includes four peroxidases, revRbr2, FdpF. These likely contribute vegetative colon during host response. Distinct regulations are observed allowing fine tuning adaptive response Understanding mechanisms protection could shed light on how survives under conditions exacerbated inflammatory

Language: Английский

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Unraveling radiation resistance strategies in two bacterial strains from the high background radiation area of Chavara-Neendakara: A comprehensive whole genome analysis

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(6), P. e0304810 - e0304810

Published: June 10, 2024

This paper reports the results of gamma irradiation experiments and whole genome sequencing (WGS) performed on vegetative cells two radiation resistant bacterial strains, Metabacillus halosaccharovorans (VITHBRA001) Bacillus paralicheniformis (VITHBRA024) (D10 values 2.32 kGy 1.42 kGy, respectively), inhabiting top-ranking high background area (HBRA) Chavara-Neendakara placer deposit (Kerala, India). The present investigation has been carried out in context that information strategies bacteria having mid-range resistance for is inadequate. WGS, annotation, COG KEGG analyses manual curation genes helped us address possible pathways involved major domains resistance, involving recombination repair, base excision nucleotide repair mismatch antioxidant genes, which candidate could activate to survive under ionizing radiation. Additionally, with help these data, we compare strains extremely model bacterium Deinococccus radiodurans, so as find commonalities existing their one hand, also rationale behind difference D10, other. Genomic analysis VITHBRA001 VITHBRA024 further ascertain capability between strains. Significantly, such uvsE (NER), frnE (protein protection), ppk1 ppx (non-enzymatic metabolite production) those carotenoid biosynthesis, are endogenous VITHBRA001, but absent VITHBRA024, explain former's better resistance. Further, this first-time study any population an HBRA. brings forward species whose not reported thus far, add knowledge capabilities phylum Firmicutes abundantly observed extreme environment.

Language: Английский

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From ubiquity to specificity: The diverse functions of bacterial thioredoxin systems

Environmental Microbiology, Journal Year: 2024, Volume and Issue: 26(6)

Published: June 1, 2024

Abstract The thioredoxin (Trx) system, found universally, is responsible for the regeneration of reversibly oxidized protein thiols in living cells. This system made up a Trx and reductase, it plays central role maintaining thiol‐based redox homeostasis by reducing thiols, such as disulfide bonds proteins. Some Trxs also possess chaperone function that independent thiol‐disulfide exchange, addition to their reductase activity. These two activities are involved numerous physiological processes bacteria. review describes diverse roles have emerged throughout bacterial evolution. essential responding oxidative nitrosative stress. Beyond this primary function, participates regulation signal transduction, controlling metabolism, motility, biofilm formation, virulence. range functions has evolved alongside diversity lifestyles specific constraints. evolution can be characterized multiplication systems specialization cofactors or targets adapt constraints atypical lifestyles, photosynthesis, insect endosymbiosis, spore‐forming

Language: Английский

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Unique growth and morphology properties of Clade 5Clostridioides difficilestrains revealed by single-cell time-lapse microscopy

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 14, 2024

Abstract Clostridioides difficile is a major One Health threat as gastrointestinal pathogen of both humans and agricultural animals. The C. species consists five main clades, with Clade 5 currently undergoing speciation from Clades 1-4. Notably, strains are highly prevalent in animals can cause zoonotic infections, suggesting that have evolved phenotypes distinguish them 1-4 strains. Here, we compare the growth properties to 1, 2, 4 using anaerobic time-lapse microscopy coupled automated image analysis. These analyses reveal grow faster than more likely form long chains cells. Comparative genomic revealed orientation invertible cmr switch sequence drives cell chaining phenotype during rich media. Interestingly, murine infection, high frequency ON shifted largely OFF state, state may be positively selected infection. Taken together, our data suggest distinct allow inhabit diverse ecological niches. Importance so phylogenetically divergent they almost meet threshold being species. Although these ubiquitously isolated environmental settings an important source community-acquired it unclear whether phenotypic efficiently colonize hosts or persist environment. By combining novel method analysis, discovered other clades frequently chains. appear driven by environmentally responsive expression non-canonical signal transduction system, which also found against mice. Collectively, promote their persistence

Language: Английский

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Critical Involvement of the Thioredoxin Reductase Gene (trxB) in Salmonella Gallinarum-Induced Systemic Infection in Chickens

Microorganisms, Journal Year: 2024, Volume and Issue: 12(6), P. 1180 - 1180

Published: June 11, 2024

Salmonella enterica serovar Gallinarum biovar (SG) causes fowl typhoid, a notifiable infectious disease in poultry. However, the pathogenic mechanism of SG-induced systemic infection chickens remains unclear. Thioredoxin reductase (TrxB) is redox protein crucial for regulating various enzyme activities serovar, but role chicken has yet to be determined. Here, we constructed mutant SG strain lacking trxB gene (trxB::Cm) and used embryo inoculation oral investigate pathogenicity SG. Our results showed that trxB::Cm exhibited no apparent differences colony morphology growth conditions reduced tolerance H2O2 increased resistance bile acids. In model, there was significant difference wild-type (WT) strains. infection, WT-infected group typical clinical symptoms with complete mortality between days 6 9 post infection. contrast, 100% survival rate, or pathological changes observed. The viable bacterial counts liver spleen trxB::Cm-infected were significantly reduced, accompanied by decreased expression cytokines chemokines (IL-1β, IL-6, IL-12, CXCLi1, TNF-α, IFN-γ), which lower than those WT group. These show trxB-deficient attenuated, indicating virulence factor chickens, suggesting may become potentially effective target controlling preventing chickens.

Language: Английский

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Adaptation mechanisms of Clostridioides difficile to auranofin and its impact on human gut microbiota

npj Biofilms and Microbiomes, Journal Year: 2024, Volume and Issue: 10(1)

Published: Sept. 17, 2024

Auranofin (AF), a former rheumatoid polyarthritis treatment, gained renewed interest for its use as an antimicrobial. AF is inhibitor of thioredoxin reductase (TrxB), thiol and protein repair enzyme, with antibacterial activity against several bacteria including C. difficile, enteropathogen causing post-antibiotic diarrhea. Several studies demonstrated the effect on difficile physiology, but crucial questions resistance mechanisms impact microbiota remain unaddressed. We explored potential by studying TrxB multiplicity generating characterizing adaptive mutations. showed that if mutants inactivated trxB genes have lower MIC AF, number TrxBs naturally present in clinical strains does not MIC. All stable mutations isolated after long-term exposure were anti-sigma factor σ

Language: Английский

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