Proteomics

Dataset Information

0

A Bacteroides fragilis protease activates host PAR2 to induce intestinal pain and inflammation

ABSTRACT: Protease-activated receptor 2 (PAR2) is a central regulator of intestinal barrier function, inflammation and pain. Upregulated intestinal proteolysis and PAR2-signaling are implicated in inflammatory bowel diseases (IBDs) and irritable bowel syndrome (IBS), conditions often associated with gut microbiome alterations. To identify potential bacterial regulators of PAR2 activity, we developed a functional assay for PAR2 processing and screened a library of diverse gut microbes. We found that multiple bacteria secrete proteases that cleave host PAR2. Using chemoproteomic profiling with a covalent irreversible inhibitor, we uncovered a previously uncharacterized Bacteroides fragilis serine protease 1 (Bfp1) and show that it cleaves and activates PAR2 in multicellular and murine models. PAR2 cleavage by Bfp1 disrupts the intestinal barrier, sensitizes nociceptors, and triggers colonic inflammation and abdominal pain. Collectively, our findings uncover Bfp1-mediated PAR2-processing as a new axis of host-commensal-interaction in the gut that has the potential to be targeted for therapeutic intervention in IBD or IBS.

INSTRUMENT(S):

ORGANISM(S): Bacteroides Fragilis (strain Atcc 25285 / Nctc 9343)

SUBMITTER: Markus Lakemeyer  

LAB HEAD: Matthew Bogyo

PROVIDER: PXD059166 | Pride | 2025-09-28

REPOSITORIES: Pride

Json Xml

Dataset's files

Source:
Action DRS
Bacteroidesfragilis_NCTC9343_chromosome-plasmid-isoforms.fasta Fasta
Bogyo_11635_1_MLB174_B.fragilis.raw Raw
checksum.txt Txt
mqpar.xml Xml
txt.zip Other
Items per page:
1 - 5 of 5
altmetric image

Publications

Protease-activated receptor 2 (PAR<sub>2</sub>) is a central regulator of intestinal barrier function, inflammation, and pain. Upregulated intestinal proteolysis and PAR<sub>2</sub> signaling are implicated in inflammatory bowel diseases (IBDs) and irritable bowel syndrome (IBS), conditions often associated with gut microbiome alterations. To identify potential bacterial regulators of PAR<sub>2</sub> activity, we developed a functional assay for PAR<sub>2</sub> processing to screen a library of  ...[more]

Similar Datasets

Other Colonic Gene expression in mice colonized with human gut microbiota from healthy and IBS patients
2017-03-02 | GSE61841 | GEO
Transcriptomics Identification of gender-determined epigenetic profiles in the pathophysiology of irritable bowel syndrome
2024-02-15 | E-MTAB-10158 | biostudies-arrayexpress
Genomics Multiple omics analysis indicated the potential role of miRNAs and target genes in visceral hypersensitivity in IBS-D
2023-03-15 | GSE212720 | GEO
Transcriptomics Expression of mRNA in intestinal tissue samples from IBS-D patients and healthy subjects
2023-03-15 | GSE212719 | GEO
Transcriptomics A preclinical model of irritable bowel syndrome driven by CHRM3 activation
2025-02-19 | GSE289595 | GEO
Transcriptomics Distinct actions of the cold water on host metabolism, gut barrier and microbiome-metabolites gut-brain modules in mice
2024-06-21 | GSE178571 | GEO
Transcriptomics Transcription profiling of human healthy volunteers and IBS patients
2009-02-21 | E-GEOD-14841 | biostudies-arrayexpress
Proteomics Colonic proteome signature in immunoproteasome-deficient stressed mice and its relevance for irritable bowel syndrome
2018-12-05 | PXD011199 | Pride
Transcriptomics Diet-induced modifications to human microbiome reshape colonic homeostasis in irritable bowel syndrome (RNA-Seq I)
2022-10-14 | GSE215048 | GEO
Other Diet-induced modifications to human microbiome reshape colonic homeostasis in irritable bowel syndrome (16S)
2022-10-14 | GSE215047 | GEO