Role of bacterial proteinases in matrix destruction and modulation of host responses

• Published in: Periodontology 2000 Vol. 24; no. 1; pp. 153 - 192
• Main Authors: POTEMPA, JAN, BANBULA, AGNIESZKA, TRAVIS, JIM
• Format: Journal Article
• Language: English
• Published: Copenhagen Munksgaard International Publishers 01.10.2000
• Subjects: Adhesins, Bacterial; Aggregatibacter actinomycetemcomitans - enzymology; Aggregatibacter actinomycetemcomitans - pathogenicity; Amino Acid Sequence; Bacteria, Anaerobic - enzymology; Bacteria, Anaerobic - pathogenicity; Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacteroides - enzymology; Bacteroides - pathogenicity; Cysteine Endopeptidases - chemistry; Cysteine Endopeptidases - genetics; Cysteine Endopeptidases - metabolism; Dental Plaque - microbiology; Dentistry; Endopeptidases - chemistry; Endopeptidases - genetics; Endopeptidases - metabolism; Extracellular Matrix Proteins - metabolism; Gene Expression Regulation, Enzymologic; Hemagglutinins - chemistry; Hemagglutinins - genetics; Hemagglutinins - metabolism; Humans; Matrix Metalloproteinases - biosynthesis; Matrix Metalloproteinases - genetics; Microbial Collagenase - genetics; Microbial Collagenase - metabolism; Molecular Sequence Data; Periodontitis - enzymology; Periodontitis - immunology; Periodontitis - microbiology; Porphyromonas gingivalis - enzymology; Porphyromonas gingivalis - pathogenicity; Treponema - enzymology; Treponema - pathogenicity
• ISSN: 0906-6713; 1600-0757
• DOI: 10.1034/j.1600-0757.2000.2240108.x

Recently accumulated large bodies of evidence have strongly implicated proteolytic enzymes released by subgingival plaque bacteria in the pathogenicity of periodontal disease. With regard to proteolytic power, however, the contribution from different microbial species considered as periodontal pathogens is not equal. Two of these bacteria, P. gingivalis and T. denticola, have developed an elaborate proteolytic systems composed of several surface-located or secreted enzymes, which apparently serve a role to provide bacteria with nutrients in the form of small peptides and amino acids. Of these two species, proteinases of P. gingivalis are the most intensively studied, and during the last decade an impressive array of information has been accumulated with respect to the biochemical characterization of purified proteinases and structure of the genes encoding them, the regulation of expression and the effects of these enzymes on host systems. In addition, studies on proteinase-deficient isogenic mutants has shed light on both their housekeeping functions and potential role(s) in the pathogenicity of periodontitis. Among several proteinases produced by P. gingivalis, the cysteine proteinases, referred to as gingipains, are clearly in the spotlight. They are the subject of several recent reviews and generally considered as the major virulence factors of this periodontal pathogen (59, 105, 139, 182, 183, 186, 281, 284, 286, 289). Gingipains seem to be key players in subverting host defense systems with, significantly, the complement and neutrophils being the main target. In addition, through uncontrolled activation of kallikrein/kinin pathway and coagulation cascade they contribute to local generation of bradykinin and thrombin, two synergistically working pro-inflammatory reagents with a strongly, although indirectly, stimulatory effect on bone resorption. Furthermore, the ability to interact with the cytokine networking systems has the potential to dysregulate the local inflammatory reaction. Finally, gingipains have a strong effect on mechanisms controlling host matrix metalloproteinase activity at the level of gene expression and zymogen activation (Fig. 10). Collectively, at the periodontal lesion site, the non-restrained action of gingipains, supported by other proteinases locally produced by subgingival plaque bacteria, would dysregulate most mechanisms controlling inflammatory reaction. Although successful in limiting infection to the periodontium, the ultimate effect of uncontrolled inflammatory processes would be the destruction of periodontal connective tissue, certainly the hallmark of periodontitis.