Implications of Porphyromonas gingivalis peptidyl arginine deiminase and gingipain R in human health and diseases

Abstract

Porphyromonas gingivalis is a major pathogenic bacterium involved in the pathogenesis of periodontitis. Citrullination has been reported as the underlying mechanism of the pathogenesis, which relies on the interplay between two virulence factors of the bacterium, namely gingipain R and the bacterial peptidyl arginine deiminase. Gingipain R cleaves host proteins to expose the C-terminal arginines for peptidyl arginine deiminase to citrullinate and generate citrullinated proteins. Apart from carrying out citrullination in the periodontium, the bacterium is found capable of citrullinating proteins present in the host synovial tissues, atherosclerotic plaques and neurons. Studies have suggested that both virulence factors are the key factors that trigger distal effects mediated by citrullination, leading to the development of some non-communicable diseases, such as rheumatoid arthritis, atherosclerosis, and Alzheimer’s disease. Thus, inhibition of these virulence factors not only can mitigate periodontitis, but also can provide new therapeutic solutions for systematic diseases involving bacterial citrullination. Herein, we described both these proteins in terms of their unique structural conformations and biological relevance to different human diseases. Moreover, investigations of inhibitory actions on the enzymes are also enumerated. New approaches for identifying inhibitors for peptidyl arginine deiminase through drug repurposing and virtual screening are also discussed.

Bacterial biofilm accumulation on self-ligating vs. elastomeric metal brackets: A review study

“…Six of these articles were appropriate for the final analysis because they assessed clinical and periodontal factors resulting from bacterial adhesion in patients with C and SL brackets. Within the confines of this investigation, it was determined that there is no proof that the kind of bracketconventional or self-ligating-has any bearing on the development of S. mutans colonies or their adherence [8,27,43,44].…”

Porphyromonas gingivalis, a bridge between oral health and immune evasion in gastric cancer

“…Furthermore, gingipain degrades proinflammatory cytokines such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-12, IL-8, IL-6, and their receptors, altering host defense mechanisms associated with inflammation. It also activates matrix metalloproteinases (MMPs), such as MMP-1, MMP-3, and MMP-9, conferring an aggressive, invasive, and prometastatic state to tumor cells ( 47 , 48 ).…”

Metabolism of periodontal pathobionts: Their regulatory roles in the dysbiotic microbiota

“…Ammonia and carbon dioxide (CO 2 ) are common end‐products of bacterial arginine metabolism, which can modulate the oxygen concentration and contribute to the alkalinity of the subgingival niche (Takahashi, 2015). The peptidylarginine deiminase expressed by P. gingivalis can convert arginine residues on host proteins to citrullinated residues and generate free ammonia (Chow et al., 2022). The ArcA system serves as a primary route for alkali generation by oral streptococci by acting on free arginine to generate ornithine, CO 2 , and ammonia.…”