Genomic repertoires linked with pathogenic potency of arthritogenic Prevotella copri isolated from the gut of patients with rheumatoid arthritis

Nii, Takuro; Maeda, Yukihide; Motooka, Daisuke; Naito, Mariko; Matsumoto, Yuki; Ogawa, Takao; Oguro, Eri; Kishikawa, Toshihiro; Yamashita, Makoto; Koizumi, Satoshi; Kurakawa, Takashi; Okumura, Ryu; Kayama, Hisako; Murakami, Masatoshi; Sakaguchi, Taiki; Das, Bhabatosh; Nakamura, Shota; Okada, Yukinori; Kumanogoh, Atsushi; Takeda, Kiyoshi

doi:10.1136/ard-2022-222881

Cited by 45 publications

(14 citation statements)

References 48 publications

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“…Here, we identified an S. copri-specific intergenic non-coding sRNA that is essential for gut colonization. S. copri presence has been associated with the onset of 21 rheumatoid arthritis in humans 12,15 and certain S. copri isolates have been shown to exacerbate the disease in a mouse model 16 . SrcF presents an ideal gene target for the precision editing of microbiomes carrying problematic S. copri strains.…”

Section: Discussionmentioning

confidence: 99%

“…Yet, the S. copri complex is less prevalent in Westernized societies 5,11 , where its presence has been disparately associated with inflammatory diseases [12][13][14][15][16] or health-beneficial effects 17 . On the former, the presence of S. copri seems to correlate with the onset of rheumatoid arthritis in humans 12,15 and certain S. copri isolates exacerbate this disease in a mouse model 16 . On the latter, the presence of Segatella spp.…”

Section: Introductionmentioning

confidence: 99%

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The RNA landscape of the human commensalSegatella coprireveals a small RNA essential for gut colonization

El Mouali,

Tawk,

Huang

et al. 2024

Preprint

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The bacterium Segatella copri is a prevalent member of the human gut microbiota associated with both health and disease states but intrinsic factors that determine its ability to effectively colonize the gut are not understood. By extensive transcriptome mapping of S. copri and examining human-derived samples, we discover a previously unknown small RNA named here Segatella RNA colonization factor (SrcF). We show that SrcF is essential for S. copri to colonize the gut in a gnotobiotic mouse model. SrcF regulates genes involved in nutrient acquisition, and its expression is controlled by complex carbohydrates, particularly fructans. Furthermore, SrcF expression is strongly influenced by human microbiome composition and by breakdown of fructans by cohabitating commensals, suggesting that the breakdown of complex carbohydrates breakdown mediates inter-species signaling among commensals beyond its established function in generating energy. Together, this study highlights the contribution of a small RNA as a key regulator in gut colonization.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The RNA landscape of the human commensalSegatella coprireveals a small RNA essential for gut colonization

El Mouali,

Tawk,

Huang

et al. 2024

Preprint

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“…For example, Prevotella copri can induce pro-inflammatory Th17 and Th1 cell immune responses, which are related to the development of rheumatoid arthritis. 37 HC group may contain many beneficial species in Prevotellaceae. There is a decrease in beneficial bacteria and an increase in harmful bacteria in the BP group, but the decreasing trend is greater than the increasing trend.…”

Section: Discussionmentioning

confidence: 99%

“…Some species can disrupt the balance of the immune system, leading to the occurrence or exacerbation of some autoimmune diseases. For example, Prevotella copri can induce pro‐inflammatory Th17 and Th1 cell immune responses, which are related to the development of rheumatoid arthritis 37 . HC group may contain many beneficial species in Prevotellaceae.…”

Section: Discussionmentioning

confidence: 99%

Identification of gut microbiota dysbiosis in bullous pemphigoid under different disease activity

Hu,

Wu,

Fan

et al. 2023

Experimental Dermatology

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Bullous pemphigoid (BP) is a severe autoimmune blistering disease affecting patients' quality of life. Gut microbiota (GM) dysbiosis have been investigated to be associated with multiple autoimmune diseases. However, the relationship between GM and BP onset and remission remains to be established by a systematic study. We conducted a study that enrolled 24 patients with BP onset (BP group), 24 patients under remission stage (BP‐R group) and 24 healthy controls (HC group). We applied 16S rRNA sequencing on faecal samples and revealed a separation of the microbiota structure. At the family level, Lachnospiraceae, Prevotellaceae and Veillonellaceae were more abundant in the HC and BP‐R groups, while Bacteroidaceae, Ruminococcaceae and Enterobacteriaceae were more abundant in the BP group. Bugbase analysis revealed the potentially pathogenic bacteria had an increasing trend in the BP group compared with the HC group and this variation vanished in the BP‐R group. At the amplicon sequence variants (ASV) level, Bacteroides ovatus (ASV40) and Veillonella dispar (ASV140) significantly decreased, while Prevotella copri (ASV54) increased in the BP group compared to the HC and BP‐R groups. The HC group and BP‐R group shared similar abundance. Furthermore, by correlation analysis, we investigated key ASVs correlated with clinical parameters and found some discriminate biomarkers between the BP and BP‐R groups. Our study established a dynamic GM profile in BP patients under different disease activity, providing a new direction to understand the role of GM in BP pathogenesis and therapeutic effects.

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“…However, these two NrdDs lack an ATP-cone and the structural basis for allosteric activity regulation in the class III RNRs is still an outstanding question. Here, we present structural, biochemical and biophysical studies on the ATP-cone-containing NrdD from the human pathogen (Nii & al., 2023) Prevotella copri (PcNrdD), showing that the binding of dATP causes increased flexibilityof the C-terminal glycyl radical-bearing domain, as well as a flap-like loop that binds across the top of the active site in the active form. This increase in dynamics is coupled to enzymatic inactivation by inhibition of substrate binding and radical transfer.…”

Section: Introductionmentioning

confidence: 99%

Activity modulation in anaerobic ribonucleotide reductases: nucleotide binding to the ATP-cone allosterically mediates substrate binding to the active site

Bimaï

Banerjee

Grinberg

et al. 2023

Preprint

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A small, nucleotide-binding domain, the ATP-cone, is found at the N-terminus of most ribonucleotide reductase (RNR) catalytic subunits. By binding ATP or dATP it regulates the enzyme activity of all classes of RNR. Functional and structural work on aerobic RNRs has revealed a plethora of ways in which dATP inhibits activity by inducing oligomerization and preventing a productive radical transfer from one subunit to the active site in the other. Anaerobic RNRs, on the other hand, store a stable glycyl radical next to the active site and the basis for their dATP-dependent inhibition is completely unknown. We present biochemical, biophysical and structural information on the effects of ATP and dATP binding to the anaerobic RNR from Prevotella copri. The enzyme exists in a dimer-tetramer equilibrium biased towards dimers when two ATP molecules are bound and tetramers when two dATP molecules are bound. In the presence of ATP, P. copri NrdD is active and has a fully ordered glycyl radical domain (GRD) in one monomer of the dimer. Binding of dATP to the ATP-cone results in loss of activity and disordering of the GRD. The glycyl radical is formed even in the dATP-bound form, but the substrate does not bind, suggesting that dATP inhibition in anaerobic RNRs acts by disordering of the GRD more than 30 Å away from the dATP molecule, thereby preventing both substrate binding and radical mobilisation. The structures implicate a complex network of activity regulation involving the GRD, the allosteric substrate specificity site and a conserved but previously unseen flap over the active site.

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Genomic repertoires linked with pathogenic potency of arthritogenic Prevotella copri isolated from the gut of patients with rheumatoid arthritis

Cited by 45 publications

References 48 publications

The RNA landscape of the human commensalSegatella coprireveals a small RNA essential for gut colonization

The RNA landscape of the human commensalSegatella coprireveals a small RNA essential for gut colonization

Identification of gut microbiota dysbiosis in bullous pemphigoid under different disease activity

Activity modulation in anaerobic ribonucleotide reductases: nucleotide binding to the ATP-cone allosterically mediates substrate binding to the active site

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