Adherence of Porphyromonas gingivalis to matrix proteins via a fimbrial cryptic receptor exposed by its own arginine‐specific protease

Abstract

SummaryPorphyromonas gingivalis, a Gram-negative anaerobe, is known to be involved in the pathogenesis of periodontitis. P. gingivalis fimbriae, which are proteinaceous appendages extending from the cell surface, may contribute to the adherence of the organism to the host cell surface. We previously suggested that arginine-specific protease produced by P. gingivalis enhanced the adherence of purified fimbriae to fibroblasts or matrix proteins. In this study, we have revealed the mechanism of the enhanced binding of fimbriae by the protease in more detail. Arg-specific protease and fimbriae were obtained from P. gingivalis 381 cells and purified. We then analysed the interaction of fimbriae and immobilized fibronectins (intact or partially degraded fibronectin by the purified protease) by using the real-time biomolecular interaction analysis (BIAcore) system with an optical biosensor based on the principles of surface plasmon resonance. BIAcore profiles demonstrated an enhanced interaction between fimbriae and protease-degraded fibronectin. We also showed specific binding of fimbriae to the degraded fibronectin by means of BIAcore analysis. The binding of biotinylated fimbriae to immobilized fibronectin was examined by enzymelinked biotin-avidin assay. The purified protease enhanced the fimbrial binding to the immobilized fibronectin. The enhancement was inhibited by the addition of L-Arg, or oligopeptides containing the Arg residue at the C-terminus in the fimbrial binding reaction, suggesting that the P. gingivalis fimbriae may potentially have an ability to bind tightly to the Arg residue at C-terminus. Taken together, these studies indicate that P. gingivalis arginine-specific protease can expose a cryptitope in the matrix protein molecules, i.e. the C-terminal Arg residue of the host matrix proteins, so that the organism can adhere to the surface layer in the oral cavity through fimbriae-Arg interaction (a novel host-parasite relationship).

The role of the RgpA–Kgp proteinase–adhesin complexes in the adherence of Porphyromonas gingivalis to fibroblasts

“…Considered together, these results suggest that the Arg-and/or Lys-specific proteinases may mediate adherence through cleaving hidden or latent surface receptors on MRC-5 cells to which the RgpA-Kgp complexes then adhere through their adhesin domains. This mechanism is similar to that previously described for P. gingivalis W50 adherence to fibronectin (Kontani et al, 1997) and epithelial cells (Pathirana et al, 2007).…”

Differential ability of periodontopathic bacteria to modulate invasion of human gingival epithelial cells by Porphyromonas gingivalis

“…To invade host cells that are not professional phagocytes, pathogens utilize diverse molecules and strategies. It has been suggested that functional epitopes of cellular receptors of P. gingivalis are cryptic, and that bacterial protease expose them [24]. The ability of various bacteria in the microbial complex of the gingival sulcus to express surface molecules to specifically interact with other bacterial species and host cells has been suggested to be a critical determinant in plaque formation and structure [19].…”

Identification of protease and rpoN-associated genes of uropathogenic Proteus mirabilis by negative selection in a mouse model of ascending urinary tract infection

“…Extracellular bacterial proteases from a number of pathogenic organisms have been demonstrated to play important roles in virulence. By degrading host tissue substrates like collagen, fibronectin and proteinaceous receptors, these enzymes can destroy host mucosal or skin barriers (Hase & Finkelstein, 1993) and promote pathogen colonization (Kontani et al, 1997). By degrading immunoglobulin or serum complement components, they may also avoid the host immune response (Hase & Finkelstein, 1993).…”