Intracellular offspring released from SFB filaments are flagellated

Nkamba, Iris; Mulet, Céline; Dubey, Gyanendra P.; Gorgette, Olivier; Couesnon, Aurélie; Salles, Audrey; Moya‐Nilges, Maryse; Jung, Vincent; Gaboriau-Routhiau, Valérie; Guerrera, Ida Chiara; Shima, Tatsuichiro; Umesaki, Yoshinori; Nigro, Giulia; Krijnse‐Locker, Jacomine; Bérard, M; Cerf‐Bensussan, Nadine; Sansonetti, Philippe J.; Schnupf, Pamela

doi:10.1038/s41564-019-0608-1

Cited by 4 publications

(3 citation statements)

References 21 publications

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“…To further confirm the local microbiome change, SFB and Lactobacillus species were detected using qPCR analysis of ileum samples collected from CPT‐treated mice (Figure 1G ), which identified a significantly higher amount of SFB and lower Lactobacillus species abundance in the ileum after the treatment. We also used a previously validated SFB ‐specific probe [ 23 ] to visualize the local bacterial changes in the ileum using the fluorescence in situ hybridization (FISH) analysis. Consistent with the previous findings, relatively few bacteria were located in the interfold region.…”

Section: Resultsmentioning

confidence: 99%

Low‐Dose Chemotherapy Preferentially Shapes the Ileal Microbiome and Augments the Response to Immune Checkpoint Blockade by Activating AIM2 Inflammasome in Ileal Epithelial Cells

Pu,

Li,

et al. 2024

Advanced Science

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Intervention of the gut microbiome is a promising adjuvant strategy in cancer immunotherapy. Chemotherapeutic agents are recognized for their substantial impacts on the gut microbiome, yet their therapeutic potential as microbiome modulators remains uncertain, due to the complexity of microbiome‐host‐drug interactions. Here, it is showed that low‐dose chemotherapy preferentially shapes the ileal microbiome to augment the extraintestinal immune response to anti‐programmed death‐1 (anti‐PD‐1) therapy without causing intestinal toxicity. Mechanistically, low‐dose chemotherapy causes DNA damage restricted to highly‐proliferative ileal epithelial cells, resulting in the accumulation of cytosolic dsDNA and the activation of the absent in melanoma 2 (AIM2) inflammasome. AIM2‐dependent IL‐18 secretion triggers the interplay between proximal Th1 cells and Paneth cells in ileal crypts, impairing the local antimicrobial host defense and resulting in ileal microbiome change. Intestinal epithelium‐specific knockout of AIM2 in mice significantly attenuates CPT‐11‐caused IL‐18 secretion, Paneth cell dysfunction, and ileal microbiome alteration. Moreover, AIM2 deficiency in mice or antibiotic microbial depletion attenuates chemotherapy‐augmented antitumor responses to anti‐PD1 therapy. Collectively, these findings provide mechanistic insights into how chemotherapy‐induced genomic stress is transduced to gut microbiome change and support the rationale of applying low‐dose chemotherapy as a promising adjuvant strategy in cancer immunotherapy with minimal toxicity.

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Section: Resultsmentioning

confidence: 99%

Low‐Dose Chemotherapy Preferentially Shapes the Ileal Microbiome and Augments the Response to Immune Checkpoint Blockade by Activating AIM2 Inflammasome in Ileal Epithelial Cells

Pu,

Li,

et al. 2024

Advanced Science

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“…The presence of nine different flagellin genes may be crucial for establishing host specificity and interactions with the fish immune system. Segmented filamentous bacteria (SFB), common members of vertebrate intestinal communities, have multiple flagellin genes in their genomes ( 67 , 68 ). Flagella are present when newly emerged offspring establish their connection to the host epithelium.…”

Section: Resultsmentioning

confidence: 99%

The exceptional form and function of the giant bacterium Ca. Epulopiscium viviparus revolves around its sodium motive force

Sannino,

Arroyo,

Pepe-Ranney

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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Epulopiscium spp. are the largest known heterotrophic bacteria; a large cigar-shaped individual is a million times the volume of Escherichia coli . To better understand the metabolic potential and relationship of Epulopiscium sp. type B with its host Naso tonganus , we generated a high-quality draft genome from a population of cells taken from a single fish. We propose the name Candidatus Epulopiscium viviparus to describe populations of this best-characterized Epulopiscium species. Metabolic reconstruction reveals more than 5% of the genome codes for carbohydrate active enzymes, which likely degrade recalcitrant host-diet algal polysaccharides into substrates that may be fermented to acetate, the most abundant short-chain fatty acid in the intestinal tract. Moreover, transcriptome analyses and the concentration of sodium ions in the host intestinal tract suggest that the use of a sodium motive force (SMF) to drive ATP synthesis and flagellar rotation is integral to symbiont metabolism and cellular biology. In natural populations, genes encoding both F-type and V-type ATPases and SMF generation via oxaloacetate decarboxylation are among the most highly expressed, suggesting that ATPases synthesize ATP and balance ion concentrations across the cell membrane. High expression of these and other integral membrane proteins may allow for the growth of its extensive intracellular membrane system. Further, complementary metabolism between microbe and host is implied with the potential provision of nitrogen and B vitamins to reinforce this nutritional symbiosis. The few features shared by all bacterial behemoths include extreme polyploidy, polyphosphate synthesis, and thus far, they have all resisted cultivation in the lab.

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“…Recombinant DVF was expressed in Escherichia coli ( E. coli ) as described previously [ 17 ]. His-tagged DVF gene was cloned into the PSMART-I vector using the BamHI and XhoI restriction enzyme sites (Fig.…”

Section: Methodsmentioning

confidence: 99%

Desulfovibrio vulgaris interacts with novel gut epithelial immune receptor LRRC19 and exacerbates colitis

Xie,

Gu,

et al. 2024

Microbiome

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Background The overgrowth of Desulfovibrio, an inflammation promoting flagellated bacteria, has been found in ulcerative colitis (UC) patients. However, the molecular mechanism in promoting colitis remains unestablished. Methods The relative abundance Desulfovibrio vulgaris (D. vulgaris) in stool samples of UC patients was detected. Mice were treated with dextran sulfate sodium to induce colitis with or without administration of D. vulgaris or D. vulgaris flagellin (DVF), and the severity of colitis and the leucine-rich repeat containing 19 (LRRC19) signaling were assessed. The interaction between DVF and LRRC19 was identified by surface plasmon resonance and intestinal organoid culture. Lrrc19−/− and Tlr5−/− mice were used to investigate the indispensable role of LRRC19. Finally, the blockade of DVF-LRRC19 interaction was selected through virtual screening and the efficacy in colitis was assessed. Results D. vulgaris was enriched in fecal samples of UC patients and was correlated with the disease severity. D. vulgaris or DVF treatment significantly exacerbated colitis in germ-free mice and conventional mice. Mechanistically, DVF could interact with LRRC19 (rather than TLR5) in colitis mice and organoids, and then induce the production of pro-inflammatory cytokines. Lrrc19 knockdown blunted the severity of colitis. Furthermore, typhaneoside, a blockade of binding interfaces, blocked DVF-LRRC19 interaction and dramatically ameliorated DVF-induced colitis. Conclusions D. vulgaris could promote colitis through DVF-LRRC19 interaction. Targeting DVF-LRRC19 interaction might be a new therapeutic strategy for UC therapy.

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Intracellular offspring released from SFB filaments are flagellated

Cited by 4 publications

References 21 publications

Low‐Dose Chemotherapy Preferentially Shapes the Ileal Microbiome and Augments the Response to Immune Checkpoint Blockade by Activating AIM2 Inflammasome in Ileal Epithelial Cells

Low‐Dose Chemotherapy Preferentially Shapes the Ileal Microbiome and Augments the Response to Immune Checkpoint Blockade by Activating AIM2 Inflammasome in Ileal Epithelial Cells

The exceptional form and function of the giant bacterium Ca. Epulopiscium viviparus revolves around its sodium motive force

Desulfovibrio vulgaris interacts with novel gut epithelial immune receptor LRRC19 and exacerbates colitis

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