PXD059166

PXD059166 is an original dataset announced via ProteomeXchange.

Title	A Bacteroides fragilis protease activates host PAR2 to induce intestinal pain and inflammation
Description	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.
HostingRepository	PRIDE
AnnounceDate	2025-09-28
AnnouncementXML	Submission_2025-09-28_08:13:58.795.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Markus Lakemeyer
SpeciesList	scientific name: Bacteroides fragilis (strain ATCC 25285 / NCTC 9343); NCBI TaxID: 272559;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-22 22:27:51	ID requested
⏵ 1	2025-09-28 08:13:59	announced

10.1016/j.chom.2025.09.010;

Lakemeyer M, Latorre R, Blazkova K, Wood HM, Jensen DD, Shakil N, Thomas SC, Saxena D, Mulpuri Y, Poolman D, Duran P, Keller LJ, Reed DE, Schmidt BL, Jim, é, nez-Vargas NN, Xu F, Lomax AE, Bunnett NW, Bogyo M, to induce intestinal pain and inflammation. Cell Host Microbe, 33(10):1686-1702.e11(2025) [pubmed]

submitter keyword: chemical proteomics, activity-based protein profiiling, Bacteroides fragilis

Matthew Bogyo
contact affiliation	Department of Pathology, Stanford University School of Medicine; Stanford, CA, USA
contact email	mbogyo@stanford.edu
lab head
Markus Lakemeyer
contact affiliation	Institute for Organic and Macromolecular Chemistry Friedrich-Schiller-University Jena
contact email	markus.lakemeyer@uni-jena.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/09/PXD059166

PRIDE project URI

• PRIDE
  1. PXD059166
     1. Label: PRIDE project
     2. Name: A Bacteroides fragilis protease activates host PAR2 to induce intestinal pain and inflammation