https://orcid.org/0000-0002-1497-1161
Figures & data
Figure 1. Schematic overview of the first mechanism of translocation. P. gingivalis secretes proteolytic enzymes known as gingipains (Rgp/Kgp) that degrade cell-cell adhesion molecules (yellow) and adhesion molecules (light green) that connect the cell with the extracellular matrix (ECM). In addition, P. gingivalis stimulates the fibroblasts to produce matrix metalloproteases (MMPs) that can degrade ECM molecules. These three effects combined weaken the integrity of the epithelial barrier, which allows P. gingivalis to travel between cells into deeper layers of the tissue.
Figure 2. Schematic overview of the second mechanism of translocation. The major fimbriae of P. gingivalis adhere to the β1 integrin receptor of the epithelial cells. This will lead to entry of the bacterium into an early phagosome. In order to survive within the cell, P. gingivalis makes use of the autophagy pathway of the epithelial cell to prevent being transferred to lysosomes, where P. gingivalis would be killed. Lastly, the bacterium exits the cell via the endocytic recycling pathway.
Figure 3. Schematic overview of the third mechanism of translocation. P. gingivalis is recognized by phagocytic cells such as macrophages, monocytes or dendritic cells. Toll-like receptor 4 (TLR4) recognizes the lipopolysaccharide (LPS) of P. gingivalis and subsequently phagocytoses the bacterium. Then, the phagocyte will travel back to the blood stream with P. gingivalis inside, as a ‘Trojan Horse’ mechanism.
Figure 4. Schematic overview of the fourth mechanism of translocation. C. albicans can form invasive hyphae that insert themselves between the epithelial cells. P. gingivalis can adhere to C. albicans via the Als3 protein on the hyphae of the fungi. Phagocytic cells such as macrophages are attracted to C. albicans. This allows for the phagocytes to come in close contact to the bacterium and take up P. gingivalis to travel back into the blood stream.
Figure 5. A schematic overview of the four putative mechanisms for P. gingivalis to translocate the oral mucosa or the endothelium of blood vessels. First, proteolytic enzymes known as gingipains (Rgp/Kgp) are secreted by P. gingivalis (green) and degrade cell-cell adherence molecules (yellow circles) and the extracellular matrix (ECM; light blue). The structural integrity of the oral mucosa is weakened so that P. gingivalis is able to pass in between the cells. Second, P. gingivalis can enter the cell after adherence and subsequent endocytosis and exit the cell on the other side of the epithelial layer. P. gingivalis needs to have a mechanism to be able to survive within the cell and not be degraded by phagolysosomes. It can then travel from cell to cell, migrating deeper into the tissue, eventually reaching the basal membrane, and finally the endothelial cells that line the blood vessels. Third, phagocytic cells of the host are able to pick up P. gingivalis within the tissue and transfer it over the endothelial barrier. They can then travel back into the bloodstream taking the bacterium with them. Again, P. gingivalis needs to have a mechanism to survive degradation by the phagocyte. Fourth and lastly, interaction with other microbes such as C. albicans (blue) could allow for travel across the oral mucosa due to the hyphae of C. albicans that can insert themselves between cells. P. gingivalis is able to attach to these hyphae. Macrophages may also play a role in this mechanism as they are attracted to the hyphae of C. albicans and can phagocytose the attached P. gingivalis.
