Porphyromonas gingivalis as a potential community activist for disease

Abstract

An extensive analysis of dental plaque samples over the years has led to the identification of "red" complex oral bacteria that have a strong association with each other and with disease. Consequently, these bacteria have been labeled 'periopathogens'. Studies with one of these bacteria, Porphyromonas gingivalis, have revealed that it contains several different mechanisms which either impede or modulate periodontal protective mechanisms. In a mouse model of periodontitis, it has been shown that modulation of complement function by P. gingivalis facilitates a significant change in both the amount and composition of the normal oral microbiotia. This altered oral commensal microbiota is responsible for pathologic bone loss in the mouse. Thus, P. gingivalis creates a dysbiosis between the host and dental plaque, and this may represent one mechanism by which periodontitis can be initiated. We have therefore termed P. gingivalis a keystone pathogen.

Figure.

The red complex bacterium P. gingivalis causes inflammation and bone loss by remodeling the oral commensal microbiota. (A) Studies have shown that P. gingivalis modulates innate host defense functions that can have global effects on the oral commensal community. Immune subversion of IL-8 secretion, complement activity, or TLR4 activation can result in an impaired host defense. The inability of the host to control the oral commensal microbial community in turn results in an altered oral microbial composition and an increased microbial load. This alteration from a symbiotic to a dysbiotic microbiota is responsible for pathologic inflammation and bone loss. (B) P. gingivalis, a low-abundance oral anaerobic bacterium (shown as a fimbriated reddish rod), exploits complement (depicted in red and white) and subverts leukocytes (in gray), leading to alterations in the amount and composition of the oral commensal microbiota (brown rods). Collectively, these changes disrupt host homeostasis and lead to destructive inflammatory periodontitis (indicated by the reddened/inflamed tissue and osteoclast-mediated bone erosion). The disease requires the presence of the commensal microbiota and intact complement pathways, since P. gingivalis fails to cause periodontitis in germ-free mice or in conventionally raised mice deficient in the complement anaphylatoxin receptors.