Interspecies Regulation of Virulence through Gingipain Inhibition by a Tannerella forsythia Serpin

ABSTRACT: Periodontitis is driven by dysbiotic microbial communities in which Porphyromonas gingivalis (Pg) acts as a keystone pathogen through its caspase-like fold (Clan CD) proteases, gingipains. Tannerella forsythia (Tf), another member of the periodontal pathogenic community, uniquely produces the broad-spectrum serpin termed miropin, yet its biological significance as an inhibitor in periodontal inflammation remains unclear. Here, we demonstrate that miropin directly inhibits the lysine-specific gingipain Kgp and the calpain-like protease Tpr produced by Pg, forming irreversible covalent inhibitory complexes. While recombinant native miropin impairs Pg growth, an engineered variant targeting both lysine- and arginine-specific gingipains entirely abolishes bacterial growth in a defined medium.

SUBMITTER: Miroslaw Ksiazek 

PROVIDER: S-SCDT-10_1038-S44319-026-00958-3 | biostudies-other |

REPOSITORIES: biostudies-other