Sulfamethoxazole drug stress upregulates antioxidant immunomodulatory metabolites in Escherichia coli

Park, Hyun Bong; Wei, Zheng; Oh, Joonseok; Xu, Hao; Kim, Chung Sub; Wang, Rurun; Wyche, Thomas P.; Piizzi, Grazia; Flavell, Richard A.; Crawford, Jason M.

doi:10.1038/s41564-020-0763-4

Cited by 26 publications

(25 citation statements)

References 69 publications

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“…We also analyzed well-known Gram-positive bacteria, including pathogenic vancomycin-resistant Enterococcus faecalis (VRE), Enterococcus gallinarum, 38 36 To test whether the pyrazinone family could be detected in vivo, we examined fecal samples from C57BL/6 specific pathogen free mice. 39 The mice were first treated with kanamycin to improve subsequent supplemental colonization. After treatment, the mice were inoculated with a kanamycinresistant variant of the commensal model E. coli BW25113.…”

Section: ■ Resultsmentioning

confidence: 99%

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Characterization of Autoinducer-3 Structure and Biosynthesis in E. coli

et al. 2020

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Escherichia coli is a common inhabitant of the human microbiota and a beacon model organism in biology. However, an understanding of its signaling systems that regulate population-level phenotypes known as quorum sensing remain incomplete. Here, we define the structure and biosynthesis of autoinducer-3 (AI-3), a metabolite of previously unknown structure involved in the pathogenesis of enterohemorrhagic E. coli (EHEC). We demonstrate that novel AI-3 analogs are derived from threonine dehydrogenase (Tdh) products and “abortive” tRNA synthetase reactions, and they are distributed across a variety of Gram-negative and Gram-positive bacterial pathogens. In addition to regulating virulence genes in EHEC, we show that the metabolites exert diverse immunological effects on primary human tissues. The discovery of AI-3 metabolites and their biochemical origins now provides a molecular foundation for investigating the diverse biological roles of these elusive yet widely distributed bacterial signaling molecules.

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Section: ■ Resultsmentioning

confidence: 99%

“…To test whether the pyrazinone family could be detected in vivo , we examined fecal samples from C57BL/6 specific pathogen free mice . The mice were first treated with kanamycin to improve subsequent supplemental colonization.…”

Section: Resultsmentioning

confidence: 99%

Characterization of Autoinducer-3 Structure and Biosynthesis in E. coli

et al. 2020

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“…They are widely conserved biomolecules that have probiotic and pathogenic roles played by gut bacteria. It has antioxidant and anti-inflammatory properties ( Feirer and Fuqua, 2017 ; Park et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Cecal Metabolomic Fingerprint of Unscathed Rats: Does It Reflect the Good Response to a Provocative Decompression?

et al. 2022

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On one side, decompression sickness (DCS) with neurological disorders lead to a reshuffle of the cecal metabolome of rats. On the other side, there is also a specific and different metabolomic signature in the cecum of a strain of DCS-resistant rats, that are not exposed to hyperbaric protocol. We decide to study a conventional strain of rats that resist to an accident-provoking hyperbaric exposure, and we hypothesize that the metabolomic signature put forward may correspond to a physiological response adapted to the stress induced by diving. The aim is to verify and characterize whether the cecal compounds of rats resistant to the provocative dive have a cecal metabolomic signature different from those who do not dive. 35 asymptomatic diver rats are selected to be compared to 21 rats non-exposed to the hyperbaric protocol. Because our aim is essentially to study the differences in the cecal metabolome associated with the hyperbaric exposure, about half of the rats are fed soy and the other half of maize in order to better rule out the effect of the diet itself. Lower levels of IL-1β and glutathione peroxidase (GPX) activity are registered in blood of diving rats. No blood cell mobilization is noted. Conventional and ChemRICH approaches help the metabolomic interpretation of the 185 chemical compounds analyzed in the cecal content. Statistical analysis show a panel of 102 compounds diet related. 19 are in common with the hyperbaric protocol effect. Expression of 25 compounds has changed in the cecal metabolome of rats resistant to the provocative dive suggesting an alteration of biliary acids metabolism, most likely through actions on gut microbiota. There seem to be also weak changes in allocations dedicated to various energy pathways, including hormonal reshuffle. Some of the metabolites may also have a role in regulating inflammation, while some may be consumed for the benefit of oxidative stress management.

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“…Several of these cytokines are shown to be raised in the cytokine storm associated with COVID-19. This offers a possible explanation for the observed clinical benefit by reducing neutrophil, monocyte and lymphocyte activation leading to a reduction in the risk of ARDS (Park et al, 2020).…”

Section: Fig 3 Formyl Peptide Receptors and Inflammationsmentioning

confidence: 93%

Cotrimoxazole and teicoplanin in the management of Covid-19: Pleiotropic effects, shadows and lights

Al-Kuraishy¹,

Al-Gareeb²,

Al-Buhadily³

2020

CMDR

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At present, coronavirus disease 2019 (Covid-19), caused by SARS-CoV-2 infection, has turned into a global pandemic. Comparable to the H7N9 virus, SARS-CoV-2 causes soaring mortality in elderly patients who have pre-existing chronic diseases. SARS-CoV-2 infects human epithelial cells by binding to human angiotensin-converting enzyme2 (ACE2). Multi-organ failure has been observed in some patients with severe COVID-19. TheACE2 expression profile suggests that SARS-CoV-2 infection may initiate or even directly cause organ failure. In addition to direct infection, evidence shows that an elevated inflammatory immune response is also involved in the pathogenesis of SARS-CoV-2 infection. The immunomodulatory and anti-inflammatory activity of the cotrimoxazole (CTX) and teicoplanin are seen in several studies that show the lower concentrations of plasma pro-inflammatory markers like CRP, IL6 in continuous CTX prophylaxis, suggesting its role as anti-inflammatory and immunomodulation. The present review concludes that both teicoplanin and CTX are effective in the management of Covid-19 through anti-SARS-CoV-2 and anti-inflammatory effects as well as controlling of secondary bacterial infections.

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Sulfamethoxazole drug stress upregulates antioxidant immunomodulatory metabolites in Escherichia coli

Cited by 26 publications

References 69 publications

Characterization of Autoinducer-3 Structure and Biosynthesis in E. coli

Characterization of Autoinducer-3 Structure and Biosynthesis in E. coli

Cecal Metabolomic Fingerprint of Unscathed Rats: Does It Reflect the Good Response to a Provocative Decompression?

Cotrimoxazole and teicoplanin in the management of Covid-19: Pleiotropic effects, shadows and lights

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