Life below the gum line: Pathogenic mechanisms of Porphyromonas gingivalis

Porphyromonas gingivalis, a gram-negative anaerobe, is a major etiological agent in the initiation and progression of severe forms of periodontal dise ase. All opportunistic pathogen, P. gingivalis can also exist in commensal harmony with the host, with disease episodes ensuing from a shift in the ec ological balance within the complex periodontal microenvironment. Colonizat ion of the subgingival region is facilitated by the ability to adhere to av ailable substrates such as absorbed salivary molecules, matrix proteins, ep ithelial cells, and bacteria that are already established as a biofilm on t ooth and epithelial surfaces. Binding to all of these substrates may be med iated by various regions of P. gingivalis fimbrillin, the structural subuni t of the major fimbriae. P. gingivalis is an asaccharolytic organism with a requirement for hemin (as a source of iron) and peptides for growth. At le ast three hemagglutinins and five proteinases are produced to satisfy these requirements. The hemagglutinin and proteinase genes contain extensive reg ions of highly conserved sequences, with posttranslational processing of pr oteinase gene products contributing to the formation of multimeric surface protein-adhesin complexes. Many of the virulence properties of P. gingivali s appear to be consequent to its adaptations to obtain hemin and peptides. Thus, hemagglutinins participate in adherence interactions with host cells. while proteinases contribute to inactivation of the effector molecules of the immune response and to tissue destruction. In addition to direct assaul t on the periodontal tissues, ;P, gingivalis can modulate eucaryotic cell s ignal transduction pathways, directing its uptake by gingival epithelial ce lls. Within this privileged site, P. gingivalis can replicate and impinge u pon components of the innate host defense Although a variety of surface mol ecules stimulate production of cytokines and other participants in the immu ne response, P. gingivalis may also undertake a stealth role whereby pivota l immune mediators are selectively inactivated. In keeping with its strict metabolic requirements, regulation of gene expression in P. gingivalis can he controlled at the transcriptional level. Finally, although periodontal d isease is localized to the tissues surrounding the tooth, evidence is accum ulating that infection with P. gingivalis may predispose to more serious sy stemic conditions such as cardiovascular disease and to delivery of preterm infants.