Identification of a secreted protease from Bacteroides fragilis that induces intestinal pain and inflammation by cleavage of PAR₂.

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). To identify potential bacterial regulators of PAR₂ activity, we developed a functional assay for PAR₂ processing and used it to screen conditioned media from a library of diverse gut commensal microbes. We found that multiple bacteria secrete proteases that cleave host PAR₂. Using chemoproteomic profiling with a covalent irreversible inhibitor, we identified a previously uncharacterized Bacteroides fragilis serine protease Bfp1, and showed that it cleaves and activates PAR

SUBMITTER: Lakemeyer M 

PROVIDER: S-EPMC11761754 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature