Analysis of the protease and adhesin domains of the PrpRI of Porphyromonas gingivalis.

The production of extracellular proteolytic enzymes is a widely used strategy by human parasites including bacteria, protozoa and helminths in order to ensure survival in the colonized host. The potential benefits to the organism arise through modifications to the external environment of the cell and include the release of essential nutrients, the disablement/deregulation of the host defences and the exposure of previously shielded substrata as new sites for colonization. Damage to the host may arise through direct proteolysis of structural proteins, deregulation of the inflammatory response or the compromising of the local host defences below the threshold necessary for effective defence. In order to examine these interactions and how they may be regulated in the periodontal diseases, we are examining the properties of proteases of the oral anaerobe Porphyromonas gingivalis with specificity for arginyl peptide bonds (ArgI, ArgIA and ArgIB): a family of enzymes which has been shown to exert effects on a variety of host proteins with roles in the control of inflammation and tissue homeostasis. Analysis of the gene for ArgI (protease polyprotein for ArgI-prpRI) together with structural and immunochemical studies of these 3 interrelated forms indicates that they may be regarded as critical determinants in multiple aspects of the life cycle of the organism via both proteolysis and binding processes. Together with the highly conserved nature of the gene, the data suggest that the PrpRI of P. gingivalis is an essential colonization determinant which may play an important role in the periodontal disease process.