P. Gingivalis

''Porphyromonas gingivalis'' belongs to the phylum ''Bacteroidota'' and is a nonmotile, Gram-negative, rod-shaped, anaerobic, pathogenic bacterium. It forms black colonies on blood agar.

It is found in the oral cavity, where it is implicated in periodontal disease, as well as in the upper gastrointestinal tract, the respiratory tract and the colon. It has been isolated from women with bacterial vaginosis.

Collagen degradation observed in chronic periodontal disease results in part from the collagenase enzymes of this species. It has been shown in an ''in vitro'' study that ''P. gingivalis'' can invade human gingival fibroblasts and can survive in the presence of antibiotics. ''P. gingivalis'' invades gingival epithelial cells in high numbers, in which case both bacteria and epithelial cells survive for extended periods of time. High levels of specific antibodies can be detected in patients harboring ''P. gingivalis''.

''P. gingivalis'' infection has been linked to Alzheimer's disease and rheumatoid arthritis. It contains the enzyme peptidyl-arginine deiminase, which is involved in citrullination. Patients with rheumatoid arthritis have increased incidence of periodontal disease; antibodies against the bacterium are significantly more common in these patients.

''P. gingivalis'' is divided into K-serotypes based upon capsular antigenicity of the various types. These serotypes have been the drivers of observations regarding bacterial cell to cell interactions to the associated serotype-dependent immune response and risk with pancreatic cancer.

Genome

The genome of ''P. gingivalis w''as described in 2003 revealing 1,990 open reading frames (i.e. protein-coding sequences), encoded by 2,343,479 bp, with an average G+C content of 48.3%. An estimated 463 genes are essential.

Virulence factors

Gingipain

Arg-gingipain (Rgp) and lys-gingipain (Kgp) are endopeptidase enzymes secreted by ''P. gingivalis.'' These gingipains serve many functions for the organism, contributing to its survival and virulence.

Arg-gingipains have been found to play a key role in the collection of nutrients for ''P. gingivalis'' survival. Rgp degrades large peptides of the host organism to provide the bacterium with an abundant nitrogen and carbon source from human albumin serum. ''P. gingivalis'' can also degrade transferrin within host cells which provides the organism with an abundant iron source needed to perform multiple cellular functions.

The gingipains are also responsible for a number of necessary functions related to host invasion and colonization. Rgp gingipains are necessary for adhesion and invasion as they processed precursor proteins of long fimbriae. The ''P. gingivalis'' genes encoding RgpA, Kgp, and hemagglutinin A (HagA) were strongly expressed after incubation with ''T. denticola''. The hemagglutinin adhesion domain-containing proteins act to increase adhesive capacities of ''P. gingivalis'' with other bacterial species. They are also associated with coordinating the integrity of the biofilm in the developing and maturation phase. Lys- gingipains (Kgp) can bind to immobilized matrix proteins fibrinogen and fibronectin and may have a role in host colonization.

Gingipains also have the ability to degrade multiple signals of the host immune response. They have the ability to cleave subclass 1 and 3 IgG antibodies as well as proinflammatory cytokines such as IL-1β, IL-2, IL-6, TNF-α and IL-8 in regions of high ''P. gingivalis'' concentration, impairing host immune response function. Rgp can inhibit IL-2 accumulation in T-cells, which enables it to evade the host adaptive immune response, by modulating T-cell communication and proliferation.

Gingipains are key factors in tissue damage symptoms of periodontitis, which results from the degradation of matrix metalloproteins, collagen, and fibronectin. Degradation of these substrates interferes with interactions between host cells and the extracellular matrix, therefore impeding wound healing and causing destruction of periodontal tissues. Rgp is responsible for eliciting the host inflammatory response via the p38α MAPK transduction pathway. This response likely contributes to the inflammatory nature of periodontitis and is involved in tissue and bone destruction.

Gingipains have been associated with Alzheimer's disease (AD). Gingipains were discovered from TMAs of patients exhibiting AD brain pathology. Both RgpB and Kbp were discovered from hippocampus and cerebral cortex of AD patients and were found to be associated with tau load, a marker for AD pathology and ubiquitin, which accumulates in tau tangles and amyloid beta plaques in AD brain. ''P. gingivalis'' 16S rRNA was also discovered in the cerebral cortex and csf of AD brains. Pretreatment with gingipain inhibitors protected neuron cell degradation caused by administration of gingipains in murine model.

Capsular polysaccharide (CPS)

The encapsulated strain of ''P. gingivalis'' is much more virulent than the nonencapsulated strain in a mouse abscess model. The capsule is a capsular polysaccharide and when present down regulates cytokine production especially proinflammatory cytokines IL-1β, IL-6, IL-8, and TNF-α, indicating host evasion responses. However, other studies have found the CPS to elicit host immune responses like PMN migration and dose and time dependent expression of cell migration chemokines like MCP-1, KC, MIP-2 and RANTES in CPS-challenged murine peritoneal macrophages. These conditions are likely to contribute to the inflammatory lesions observed in periodontitis.

Vaccines made from ''P. gingivalis'' CPS apparently impair oral bone loss in murine models. These vaccines have been able to elicit potent immune responses such as increased IgM and IgG responses that recognize whole ''P. gingivalis'' organisms.

Fimbriae

Fimbriae are appendages involved in cellular attachment and greatly contribute to virulence and are found on many Gram-negative and some Gram-positive bacteria.

''P. gingivalis'' virulence is heavily associated with fimbriae as they have been characterized to be key factors in adhesion, invasion, and colonization. Fimbriae are also responsible for invasion of membrane vesicles into host cells. They were found to bind to cellular α5β1 integrins, which mediated adherence and impaired the homeostatic controls of host cells. Fimbriae were also found to be associated with modulating β2 integrin adhesive activity for uptake by monocytes using the CD14/TLR2/PI3K signaling complex, which may contribute to intracellular evasion tactics by ''P. gingivalis''. ''P. gingivalis'' has long fimbriae, short fimbriae, and accessory components, each of which have distinct functions.

Long fimbriae

Long fimbriae (FimA), also known as major fimbriae, are long, peritrichous, filamentous components. They have a role in initial attachment and organization of biofilms, as they act as adhesins that mediate invasion and colonization of host cells contributing to ''P. gingivalis'' virulence.

Short fimbriae

Short fimbriae (Mfa1), also known as minor fimbriae, have distinct roles from long fimbriae and are characterized to be essential for cell-cell auto aggregation and recruitment for microcolony