GSH Protects the Escherichia coli Cells from High Concentrations of Thymoquinone

Łyżeń, Robert; Gawron, Grzegorz; Kadziński, Leszek; Banecki, Bogdan

doi:10.3390/molecules27082546

Cited by 4 publications

(3 citation statements)

References 31 publications

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“…In particular, 14 of the genes upregulated in KO mice belong to the pathway of glutathione metabolism (eco00480), and previous studies demonstrated that glutathione metabolism is involved in protection against oxidative stress. 42 , 43 In addition, Sakamoto et al reported mprA to be involved in resistance to oxidative stress, together with the activity of gshA (glutathione synthase), which is also upregulated in our populations 40 . Additionally, our metatranscriptomic data confirm the findings of Tawk et al, suggesting a role for vitamin B6 metabolism.…”

Section: Discussionsupporting

confidence: 50%

Evolution of E. coli in a mouse model of inflammatory bowel disease leads to a disease-specific bacterial genotype and trade-offs with clinical relevance

Unni,

Andreani,

Vallier

et al. 2023

Gut Microbes

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Inflammatory bowel disease (IBD) is a persistent inflammatory condition that affects the gastrointestinal tract and presents significant challenges in its management and treatment. Despite the knowledge that within-host bacterial evolution occurs in the intestine, the disease has rarely been studied from an evolutionary perspective. In this study, we aimed to investigate the evolution of resident bacteria during intestinal inflammation and whether- and how disease-related bacterial genetic changes may present trade-offs with potential therapeutic importance. Here, we perform an in vivo evolution experiment of E. coli in a gnotobiotic mouse model of IBD, followed by multiomic analyses to identify disease-specific genetic and phenotypic changes in bacteria that evolved in an inflamed versus a non-inflamed control environment. Our results demonstrate distinct evolutionary changes in E. coli specific to inflammation, including a single nucleotide variant that independently reached high frequency in all inflamed mice. Using ex vivo fitness assays, we find that these changes are associated with a higher fitness in an inflamed environment compared to isolates derived from non-inflamed mice. Further, using large-scale phenotypic assays, we show that bacterial adaptation to inflammation results in clinically relevant phenotypes, which intriguingly include collateral sensitivity to antibiotics. Bacterial evolution in an inflamed gut yields specific genetic and phenotypic signatures. These results may serve as a basis for developing novel evolution-informed treatment approaches for patients with intestinal inflammation.

show abstract

Section: Discussionsupporting

confidence: 50%

Evolution of E. coli in a mouse model of inflammatory bowel disease leads to a disease-specific bacterial genotype and trade-offs with clinical relevance

Unni,

Andreani,

Vallier

et al. 2023

Gut Microbes

View full text Add to dashboard Cite

show abstract

“…KatG (catalase) works in concert with these dismutases as it eliminates hydrogen peroxide produced by these manganese and iron-dependent SODs ( Imlay, 2013 ). GshA is required for the biosynthesis of the antioxidant glutathione and the knockout strain is more sensitive to a range of oxygen radicals ( Łyżeń et al, 2022 ). MutT hydolyzes 8-oxo-dGTP to 8-oxo-dGMP to remove it from the nucleotide pool and prevent its misincorporation into DNA ( Ito et al, 2005 ) RecA is required for homologous recombination and is necessary for double-stranded DNA break repair arising from single and double-strand breaks generated by oxygen radicals ( Horii et al, 1980 ).…”

Section: Resultsmentioning

confidence: 99%

The antibacterial activity of a photoactivatable diarylacetylene against Gram-positive bacteria

Waite,

Adams,

Chisholm

et al. 2023

Front. Microbiol.

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The emergence of antibiotic resistance is a growing threat to human health, and therefore, alternatives to existing compounds are urgently needed. In this context, a novel fluorescent photoactivatable diarylacetylene has been identified and characterised for its antibacterial activity, which preferentially eliminates Gram-positive over Gram-negative bacteria. Experiments confirmed that the Gram-negative lipopolysaccharide-rich outer surface is responsible for tolerance, as strains with reduced outer membrane integrity showed increased susceptibility. Additionally, bacteria deficient in oxidative damage repair pathways also displayed enhanced sensitivity, confirming that reactive oxygen species production is the mechanism of antibacterial activity. This new diarylacetylene shows promise as an antibacterial agent against Gram-positive bacteria that can be activated in situ, potentially for the treatment of skin infections.

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“…Interestingly, this is also confirmed by our metatranscriptomic analysis. In particular, 14 of the genes upregulated in KO mice belong to the pathway of glutathione metabolism (eco00480), and previous studies demonstrated that glutathione metabolism is involved in protection against oxidative stress 42,43 . In addition, Sakamoto et al reported mprA to be involved in resistance to oxidative stress, together with the activity of gshA (glutathione synthase), which is also upregulated in our populations 40 .…”

Section: Discussionmentioning

confidence: 99%

Evolution ofE. coliin a mouse model of inflammatory bowel disease leads to a disease-specific bacterial genotype and trade-offs with clinical relevance

Unni,

Andreani,

Vallier

et al. 2023

Preprint

View full text Add to dashboard Cite

Objective: Inflammatory bowel disease (IBD) is a persistent inflammatory condition affecting the gastrointestinal tract, presenting significant challenges in its management and treatment. Despite the knowledge that within-host bacterial evolution occurs in the intestine, the disease has so far rarely been studied from an evolutionary perspective. In this study, we aimed to investigate resident bacterial evolution during intestinal inflammation, and whether- and how disease-related bacterial genetic changes may present trade-offs with potential therapeutic importance. Design: Here, we perform an in vivo evolution experiment of E. coli in a gnotobiotic mouse model of IBD, followed by multiomic analyses to identify disease-specific genetic and phenotypic changes in bacteria evolved in an inflamed versus non-inflamed control environment. Results: Our results demonstrate distinct evolutionary changes in E. coli specific to inflammation, including a single nucleotide variant that independently reached high frequency in all inflamed mice. Using ex vivo fitness assays, we find that these changes are associated with a higher fitness in an inflamed environment compared to isolates derived from non-inflamed mice. Further, using large-scale phenotypic assays, we show that bacterial adaptation to inflammation results in clinically relevant phenotypes, which intriguingly include collateral sensitivity towards antibiotics. Conclusions: Bacterial evolution in an inflamed gut yields specific genetic and phenotypic signatures. These results may serve as a basis for developing novel, evolution-informed treatment approaches for patients with intestinal inflammation.

show abstract

GSH Protects the Escherichia coli Cells from High Concentrations of Thymoquinone

Cited by 4 publications

References 31 publications

Evolution of E. coli in a mouse model of inflammatory bowel disease leads to a disease-specific bacterial genotype and trade-offs with clinical relevance

Evolution of E. coli in a mouse model of inflammatory bowel disease leads to a disease-specific bacterial genotype and trade-offs with clinical relevance

The antibacterial activity of a photoactivatable diarylacetylene against Gram-positive bacteria

Evolution ofE. coliin a mouse model of inflammatory bowel disease leads to a disease-specific bacterial genotype and trade-offs with clinical relevance

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