A bacterial etiology for periodontal diseases in human is widely accepted, and several bacterial species have been implicated as major pathogens due to their presence in high numbers in plaques from diseased sites and due to their pathogenic potential. It is the objective of the proposed research to study an important pathogenic property of a group of such organisms, that is, the proteolytic capacity of strains of Porphyomonas gingivalis, and the influence of such proteolytic organisms on the ability of antibacterial host defense mechanisms to be protective against infection with these organisms. Our previous studies have demonstrated that P. gingivalis activates complement but that some strains fail to accumulate complement-derived opsonins on their surface due to bacterial proteases. The strains that behave in this manner have been demonstrated to be invasive or 'virulent' in a mouse model of invasiveness. Thus, defective opsonization and failure of subsequent removal of bacteria by host phagocytes may be an important virulence factor for these organisms. First, since this property seems to be characteristic of invasive strains of P. gingivalis , a series of clinical and laboratory isolates will be tested for their failure to bind C3 fragments during complement activation due to proteolytic activity and for invasiveness. These strains will also be tested for invasiveness. Proteases will be isolated from some of these strains for the purpose of producing antibodies that can serve as inhibitors of proteolytic activity. These antibodies will be used in assays of C3 degradation, complement activation, and as promoters of deposition of C3-derived opsonins on the surfaces of bacteria that otherwise fails to accumulate C3. Furthermore, the antibodies will be used as reagents in assays of bacterial uptake by PMN's following opsonization with antibody, complement, or both. Finally, human sera with high titers of antibodies against P. gingivalis will be tested for antiprotease activity and correlated with the ability to promote complement-mediated opsonization. The studies proposed have the potential to establish the importance of P. gingivalis proteases as important virulence factors.
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