Porphyromonas gingivalis: keeping the pathos out of the biont

Abstract

The primary goal of the human microbiome initiative has been to increase our understanding of the structure and function of our indigenous microbiota and their effects on human health and predisposition to disease. Because of its clinical importance and accessibility for in vivo study, the oral biofilm is one of the best-understood microbial communities associated with the human body. Studies have shown that there is a succession of select microbial interactions that directs the maturation of a defined community structure, generating the formation of dental plaque. Although the initiating factors that lead to disease development are not clearly defined, in many individuals there is a fundamental shift from a health-associated biofilm community to one that is pathogenic in nature and a central player in the pathogenic potential of this community is the presence of Porphyromonas gingivalis. This anaerobic bacterium is a natural member of the oral microbiome, yet it can become highly destructive (termed pathobiont) and proliferate to high cell numbers in periodontal lesions, which is attributed to its arsenal of specialized virulence factors. Hence, this organism is regarded as a primary etiologic agent of periodontal disease progression. In this review, we summarize some of the latest information regarding what is known about its role in periodontitis, including pathogenic potential as well as ecological and nutritional parameters that may shift this commensal to a virulent state. We also discuss parallels between the development of pathogenic biofilms and the human cellular communities that lead to cancer, specifically we frame our viewpoint in the context of 'wounds that fail to heal'.

Keywords: P. gingivalis; biofilm; immunoediting hypothesis; pathobiont; tumor.

Fig. 1

P. gingivalis-mediated periodontitis is a biofilm associated disease of slow progression. Early within the oral cavity there is a mixed community of bacteria with an abundance of Gram-positive organisms (purple cocci). Over time (represented by the triangle at bottom), there is a maturation of the biofilm. External and internal pressures such as an anoxic environment, mammalian cell infiltrate, viral and phage activity, DNA exchange, nutrient availability, and physical and chemical interactions of the microbes, drive development. A currently unidentified event occurs that allows for the out-growth of Gram-negative organisms (red and green rods), in particular P. gingivalis (shown in green). There is also active recruitment of cells of the immune system, such as neutrophils (shown in purple) to the site, which then brings in a battery of host-derived signaling molecules, impacting the microbial community.