BACTERIAL PROTEINASES IN PERIODONTAL DISEASE

点击翻译按钮获取中文摘要

DESCRIPTION: Periodontal disease is a mixed infection, primarily involving colonization of the gingival sulcus and/or the periodontal pocket by the organism Porphyromonas gingivalis (P. gingivalis). This bacterium produces significant quantities of cysteine-class proteinases, and these are believed to be responsible for both the direct and indirect degradation of the connective tissue structure within the periodontal pocket. Two of the major proteinases released by P. gingivalis, one with Arg-X and the other with Lys-X specificity, have been purified and are suggested to be responsible for the dysregulation of the complement, kallikrein, and coagulation cascades, and as a result the increased crevicular flow, bleeding on probing, and neutrophil accumulation which are hallmarks of periodontitis. Analysis of their primary structure indicates that each proteinase is synthesized as a large polyprotein precursor which is processed into a non-covalently linked complex containing a catalytic domain and a putative adhesion/hemagglutination domain. The Specific Aims of this proposal are designed 1) to further elucidate the role of these enzymes in disrupting both the regulation of fibrinolysis and the control of host proteinases, 2) to characterize the adhesion/hemagglutinin domains of each proteinase, 3) to investigate the mechanism(s) of maturation of each proteinase from its high molecular weight poly-protein precursor form, 4) to determine the role of each proteinase in the adhesion and invasion of host epithelial cells by P. gingivalis, and 5) to begin a collaborative investigation to determine whether vaccines produced against each proteinase might be useful therapeutics.