Porphyromonas gingivalis: Local and Systemic Virulence

The asaccharolytic anaerobe Porphyromonas gingivalis is a contextually virulent keystone pathogen in the onset and progression of periodontal diseases. P. gingivalis is equipped with an array of virulence factors that promote oral colonization and adaptation to the prevailing heme and oxygen levels in the periodontal ecosystem. Interactions among the oral polymicrobial community lead to increased nososymbiocity (community pathogenicity), and P. gingivalis is adept at inducing dysbiotic inflammatory responses. In particular, the decoupling of inflammation from bacterial killing mechanisms misdirects innate immunity and provides proteinaceous metabolic substrates. The properties that underlie the success of P. gingivalis also provide the framework for its versatility as a systemic pathogen. P. gingivalis can exert a systemic influence following, for example, hematogenous spread and localization at remote tissues. Additionally, secreted bioactive components and metabolites, as well as locally generated immune effectors, have the potential to disrupt homeostasis on a systemic level. The ability to subvert epithelial cell life-and-death decisions further endows P. gingivalis with oncopathogenic properties. In this review, we first examine polymicrobial synergy, colonization, and metabolic adaptation in the periodontal niche; then analyze mechanisms of immune subversion at epithelial and myeloid interfaces; and finally discuss how these strategies contribute to periodontitis and to systemic inflammatory, autoimmune, neurodegenerative, and neoplastic diseases.