Porphyromonas gingivalis: Multiple Tools of an Inflammatory Damage

Periodontitis (periodontal disease [PD]) is a complex inflammatory disease caused by a polymicrobial infection that facilitates the destruction of the connective tissue and bone that support the teeth. PD is highly correlated with cardiovascular disease, low birth weight, preterm osteoporosis, Alzheimer's disease, and rheumatoid arthritis. Porphyromonas gingivalis, a main causative agent of PD, is a non-motile, asaccharolytic, Gram-negative bacterium identified in subgingival, supragingival, and tongue sites in patients. P. gingivalis produces an arsenal of virulence factors, which include fimbriae, lipopolysaccharide (LPS), gingipains and other proteases, P. gingivalis peptidyl arginine deiminase (PPAD), and others. Recently, a number of reports highlighted novel aspects of P. gingivalis virulence. LPS signaling via Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) was elucidated; outer membrane vesicles (OMVs) were implicated as the shuttle for inflammatory induction and neurotoxicity, and gingipains were found to disrupt the integrity of blood-brain barrier (BBB). Further, Tpr protease substrate specificity was described in detail, a novel variant of PPAD was identified and correlated with the aggressive disease, and the role of C-terminal domain as the substrate for the Type IX secretion system (T9SS) transport has been unveiled, together with the identification of the first T9SS inhibitors. The impact of the COVID-19 pandemic prompted the novel research, expanding our understanding of the P. gingivalis correlation with viral infections. These recent findings implicate the need to update the current knowledge of the P. gingivalis virulence factors and provide a comprehensive review of the current trends in P. gingivalis research.