## 3 Pathogenic Mechanisms of _P. gingivalis_
### Molecular Mimicry and Systemic Dissemination  
_P. gingivalis_ is considered a key bacterial pathogen in periodontal disease largely due to its ability to produce outer membrane vesicles (OMVs), which are released via a molecular mimicry mechanism and play a central role in its pathogenesis [34]. OMVs are spherical, bilayered structures (50-250 nm in diameter) shed from the bacterial surface during growth without compromising membrane integrity (Figures 1 and 2). These vesicles participate in essential processes such as stress adaptation, nutrient acquisition, and intercellular communication with both host tissues and microbial communities [35].  
\begin{table}
\begin{tabular}{l c} \hline
\begin{tabular}{c} Fimbirae \\ \end{tabular} \\ \hline \end{tabular}
\end{table}
Table 1: Cont.  
Figure 1: Virulence factors and related effects in _P. gingivalis_ OMVs. OMVs (outer membrane vesicles), F-actin (filamentous actin), GTPase (enzyme that hydrolyzes GTP), Rac (Rho family GTPase), PIK (phosphoinositide kinase), IL (interleukin), NO (nitric oxide), TNF (tumor necrosis factor), COX (cyclooxygenase), MMPs (matrix metalloproteinases), FAK (focal adhesion kinase), NH-K (nuclear factor kappa), IFN (interferon), TfR (transferrin receptor), PRR (pattern recognition receptor). Created with Biorender.com. (1) _P. gingivalis_ outer membrane vesicles (OMVs) can be internalized into cells by an actin-mediated pathway that utilizes host receptors, especially \(\propto\)5\(\beta\)1-integrin, which is controlled by PIJK and depends on caveolin, dynamin, and Rac1. (2) _P. gingivalis_ OMVs can be internalized into cells through the fimbria-dependent lipid raft pathway, which is dependent on PIJK and Rac1, and involves various regulatory GTPases. (3) _P. gingivalis_ OMVs can exert virulence by affecting different receptors on the host cell surface, such as activating PRR receptors and degrading TfR receptors. (4–6) _P. gingivalis_ OMVs can activate or degrade a variety of biologically active substances in host cells, inhibit cell proliferation, promote glycolysis and apoptosis, and cause host cells to produce a variety of inflammatory factors, thereby promoting the formation of an inflammatory environment.  
Figure 2: Film locus (fimbrae locus), GalE (galactose epimerase), OmpA (outer membrane protein). Production and regulation of _P. gingivalis_ outer membrane vesicles (OMVs). After the cell wall is excised, phospholipids accumulate in the outer membrane leaflets, and the expansion pressure continues to be produced, which intensifies the further enrichment of outer membrane components. The linkage between peptidoglycan and the outer membrane layer is disrupted, and finally, _P. gingivalis_ OMVs are formed. The film locus and GalE mutant strains reduced or even eliminated the production of _P. gingivalis_ OMVs, while the OmpA mutant strain overproduced _P. gingivalis_ OMVs. Created with Biorender.com.  
Compared to free bacteria, OMVs are more stable, highly adhesive, and protease-resistant, enabling them to concentrate and deliver virulence factors efficiently into the surrounding environment, thereby enhancing bacterial pathogenicity. Importantly, _P. gingivalis_-derived OMVs can enter the bloodstream and reach distant tissues, potentially contributing to systemic diseases associated with the pathogen.