Degradation of host protease inhibitors and activation of plasminogen by proteolytic enzymes from Porphyromonas gingivalis and Treponema denticola.

Bacterial proteases may participate in the pathogenesis of periodontal diseases through their action on host proteins. In the present study, the ability of selected periodontopathogens, as well as two proteases isolated from Porphyromonas gingivalis and Treponema denticola, to degrade host protease inhibitors was evaluated. The activation of human plasminogen by the two bacterial proteases was also investigated. Proteolytic breakdown of host protease inhibitors (alpha-1-antitrypsin, antichymotrypsin, alpha 2-macroglobulin, antithrombin III, antiplasmin and cystatin C) was evaluated by SDS-PAGE. The 80 kDa trypsin-like protease of P. gingivalis completely digested the six protease inhibitors under investigation, whereas the 95 kDa chymotrypsin-like protease of T. denticola was slightly less active, more particularly on alpha 2-macroglobulin and cystatin C. When whole cells from a number of oral bacterial species were tested, the most significant degradation was obtained with P. gingivalis, T. denticola, Prevotella intermedia, Prevotella nigrescens and Capnocytophaga spp. Peptostreptococcus micros and Propionibacterium acnes had only some degradative activity on selected inhibitors, whereas three bacterial species, Actinobacillus actinomycetemcomitans, Bacteroides forsythus and Fusobacterium nucleatum, had no effect on the protease inhibitors. The 80 kDa protease of P. gingivalis demonstrated strong plasminogen activation, whereas no such activity was associated with the 95 kDa protease of T. denticola. This study indicates the high potential of some periodontal pathogens to destroy protease inhibitors and activate plasminogen. This may result in an uncontrolled degradation of periodontal tissues and a rapid progression of the disease.