The contextual pathogenicity of Porphyromonas gingivalis

Porphyromonas gingivalis has long been recognized as a keystone pathogen associated with periodontal diseases and has more recently been implicated in systemic comorbidities beyond the oral cavity. However, amongst the oral microbiota, P. gingivalis has a distinctive relationship with the host, and despite possessing a repertoire of virulence factors, P. gingivalis colonization does not invariably result in adverse outcomes. Under specific ecological conditions and host immune or susceptibility states, P. gingivalis functions as a keystone pathogen, exerting an impact disproportionate to its abundance in the context of a complex polymicrobial community. Indeed, P. gingivalis-containing communities induce dysbiotic immune responses that lead to pathobiont expansion and inflammatory tissue destruction. Moreover, emerging evidence indicates that virulence in P. gingivalis is tunable in response to metabolite availability. Under nutritional limitation, cell-associated gingipain activity increases, conferring on P. gingivalis the potential to more aggressively degrade host tissues and thereby generate proteinaceous substrates for growth. In addition, P. gingivalis is adept at decoupling nutritionally favourable inflammatory responses from antimicrobial pathways. Ultimately, substrate availability and the host immune response re-equilibrate, and P. gingivalis once again becomes quiescent. In this Review, we discuss the mechanistic basis of contextual virulence regulation in P. gingivalis and its impact on host homeostasis and immune function.