The proteolytic activity of Porphyromonas gingivalis is a critical virulence factor in the murine model of periodontitis

Abstract

Porphyromonas gingivalis, a periodontal pathogen, has an inter-strain variability in virulence. We recently reported that the cell invasion ability, but not cytokine proteolytic activities, of P. gingivalis has strong positive correlations with clinical parameters of subjects who harbored the isolates. To determine the contribution of the invasion ability and proteolytic activity to the virulence of P. gingivalis in the murine model of periodontitis, three clinical isolates KUMC-P1 (P1: low cell invasion ability and low proteolytic activity), KUMC-P4 (P4: low cell invasion ability but high proteolytic activity), and KUMC-P8 (P8: high cell invasion ability but low proteolytic activity) were orally inoculated in Balb/c mice. The net alveolar bone loss induced by three strains was P4 > P8 > P1, where the difference between P8 and P1 was not significant. The amounts of P. gingivalis within the gingival tissues examined by in-situ hybridization using a P. gingivalis-specific probe were increased by all three strains, which had a significant positive correlation with alveolar bone loss. Whereas P1 and P8 induced a significant IgA antibody response, P4 induced a slight but not significant IgG1 antibody response against P. gingivalis. In vitro, P4 had the greater effect than other strains on the epithelial barrier disruption evidenced from the reduction in the levels of tight junction proteins and transepithelial resistance. In conclusion, the proteolytic activity of P. gingivalis was a critical virulence factor in the murine model of periodontitis, which may be attributed to the paracellular pathway-dependent bacterial invasion of the gingival tissue in mice.