**4. Porphyromonas gingivalis and its central role in the pathogenesis of PD**

Understanding further details of the disease process of PD from the perspective of the oral microbiome can assist in the creation of novel preventative and treatment applications.

Overall, bacteria, fungi, viruses, and protozoa are among the estimated 1000 microbial species that make up the oral microbiome. However, more than 700 microbes are bacterial, giving investigators a rationale for focusing on the bacterial taxa of the oral cavity, when examining health status [36–38].

#### *Evaluation of Trans-Resveratrol as a Treatment for Periodontitis DOI: http://dx.doi.org/10.5772/intechopen.101477*

Keystone pathogen, *P. gingivalis* (*Pg*), is a Gram-negative, anaerobic, non-motile, a-saccharolytic bacteria, which is a part of the normal flora of the subgingival region of the oral cavity, becomes an opportunistic pathogen when the microenvironmental factors permit it to thrive [39].

Also of note, is lipopolysaccharide (LPS), a feature found in the cell walls of Gram-negative bacteria, which triggers an inflammatory response as a pathogenassociated molecular pattern (PAMP). inflammation [40].

Detection by the host complement system is avoided due to the capsule, which is seen in most strains of *Pg* [41]. Also, the bacterial virulence factors, FimA and Mfa, which are proteins that make up the bacterial appendages, fimbriae, and pili, allow *Pg* to adhere to the periodontal cells whilst encouraging agglutination between bacteria, thus promoting the formation of a pathogenic biofilm [39, 42–44] (**Figure 6**).

Following adherence to the gingival epithelia, *Pg* can enter into its host cell with ease, due to the secretion of the serine phosphatase, SerB, which enters the host cell and triggers the de-polymerisation of cytoskeletal actin microfilaments [45] (**Figure 6**).

For increased success in gaining an intracellular foothold, *Pg* also employs a sophisticated secretory system (e.g., Type IX Secretory System [T9SS]), which spans the periplasmic space and allows for the passage of its secretory products from the cytoplasm into the extracellular environment [46, 47].

Further to this, gingipains are involved in the manipulation of the host immune system, making them key players in tissue destruction through chronic inflammation. For example, gingipains have been found to degrade many cytokines as well as the CD4 and CD8 integral membrane proteins of T lymphocytes, creating interference within the host's adaptive immune system [46, 48–50].

Moreover, an autoimmune attack on host tissue is assisted by the effector protein, peptidylarginine deaminase (PAD), which post-translationally modifies host proteins through citrullination, setting them up as immune targets [46, 51, 52] (**Figure 6**).

#### **Figure 6.**

*A schematic of the major virulence factors of Porphyromonas gingivalis and a general overview of their involvement in pathogenicity.*

Other significant virulence factors of *Pg* include outer membrane vesicles (OMVs), which are released from most Gram-negative bacteria and can infiltrate places that the bacteria cannot. However, those derived from *Pg*, are armed with an outer membrane layer, consisting of a capsule, LPS, and gingipains, enclosing an internal compartment loaded with effector proteins and other macromolecules such as nucleic acids. Indeed, OMVs are pro-inflammatory agents of cytotoxic destruction aiding in biofilm formation, as well as the manipulation and evasion of the host immune response [46, 53] (**Figure 6**).
