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Merinda Hall Bench B 23/09/2016 ^[1]

Classification

Higher order taxa

Bacteria – Bacteroidetes– Bacteroidia – Bacteroidales – Porphyromonadaceae – Porphyromonas

Species

Porphyromonas gingivalis 2561^T, ATCC 33277^T, CCUG 25893^T, CCUG 25928^T, CIP 103683^T, DSM 20709^T, JCM 12257^T, NCTC 11834^T.

Description and significance

Bacteroides gingivalis, first isolated by Coykendall and colleagues from human oral periodontal pockets, was recognised as a species distinct from Bacteroides asaccharolyticus in 1980 ^[1]. Along with Bacteroides endodontalis, and B. asaccharolyticus, B. gingivalis was reclassified to its current genus designation of Porphyromonas in 1988 ^[2].

Porphyromonas gingivalis is an obligately anaerobic, gram negative coccobacillus that forms black pigmented colonies in culture ^[3]. It is capsulated, non-motile, and is unable to ferment carbohydrates, requiring a complex nutritional profile to be provided in its environment for optimal growth. Hence, like other members of this genus, P. gingivalis is commonly found in the oral cavity, particularly the subgingival region. In these favourable conditions, it can form biofilms with other community members, and has been implicated in the development of periodontitis ^[4]. P. gingivalis has also been implicated in heart disease ^[5], rheumatoid arthritis ^[6], respiratory tract infections ^[7], and complications during pregnancy ^[8]. The study of this microorganism is therefore relevant to our understanding of human disease, its treatment and prevention.

Genome structure

The genome of P. gingivalis strain W83 was fully sequenced in 2003 ^[9], and the type strain 5 years later ^[10]. Several additional strains have been recently sequenced expanding the knowledge of genetic variation within this species ^[11], ^[12].

The type strain genome consists of one circular chromosome, 2,354,886 base pairs in length, with an average G+C content of 48.4%. A total of 2090 coding sequences were identified, and 53 tRNA genes, covering 86.1% of the genome ^[10]. A significant degree of genetic variation is observed between strains, for example several type strain genes are more similar to genes of other bacterial species than to the P. gingivalis strain W83. This is likely due to the conjugative ability of this species, and various other mobile genetic elements ^[10], ^[13].

Cell structure and metabolism

The peptidoglycan of the P. gingivalis cell wall differs from related genera due to use of meso-diaminopimelic acid as the lysine component ^[2]. The lipid A subunit of the lipopolysaccharide (LPS) layer is also distinctive, alternating its structure according to environmental factors - such as hemin availability – which results in variable virulence of the bacteria to host cells ^[14]. Lacking flagella or type IV pili, P. gingivalis is non-motile, though it does possess a Por secretion system which provides gliding motility to other species within the Bacteroidetes phylum. In P. gingivalis, however, it is used instead for secretion of proteases such as gingipains ^[15]. Makeup of the capsular polysaccharide of P. gingivalis is strain specific, allowing serotyping based on capsular antigens ^[16].

P. gingivalis possess fimbriae essential for colonisation of periodontal surfaces, formation of biofilms, and therefore virulence. Expression of the major fimbriae (FimA) - which mediates adhesion to host surfaces - is responsive to environmental cues, resulting in variable levels of virulence due to the temperature, hemin concentration and the salivary molecules present ^[4]. Short fimbriae (Mfa1) mediate cell-cell adhesion and are therefore important for colony formation, and adhesion to other microbial species in the formation of biofilms ^[17].

The metabolism of glucose for energy is known to be poor in P. gingivalis, and it is rather by the fermentation of a number of different amino acids that it is able to gain energy. It also preferentially uses peptides for carbon and nitrogen sources. Based on genome analysis, the major metabolites that are likely produced by P. gingivalis include acetate, butyrate, propionate, isobutyrate, isovalerate, ethanol, and butanol. The production of succinyl-CoA from glutamate and aspartate is performed via a pathway not usually found in bacterial species. Additionally, the further conversion of succinyl-CoA to butyrate and propionate appears unique to P. gingivalis ^[9]. Lastly, the observable black pigmentation of colonies is due to accumulation of μ-oxo oligomers produced from the heme of red blood cells ^[15].

Ecology

Due to the anaerobic and specific nutrient requirements of P. gingivalis, it is most commonly found in the oral cavity of humans, particularly inflamed gingival pockets, or infected root canals ^[4]. It has also been isolated in other cases of disease such as from the amniotic fluid of pregnant women ^[8] and in the lungs of pneumatic patients ^[7]. However, the anaerobic conditions produced by other species in plaque creates a particularly favourable environment, hence P. gingivalis most frequently adheres to organisms in newly formed plaque biofilms rather than directly to the tooth surface ^[4]. For example, following colonisation by gram-positive organisms, conciliatory bacteria such as Fusobacterium nucleatum bind, providing the conditions for pathogens such as P. gingivalis to join the plaque biofilm ^[14].

Pathology

The opportunistic pathogenicity and invasiveness of P. gingivalis is environment specific. While capsulation is constant and required for virulence ^[10], the expression of other virulence factors are modulated in accordance with local conditions. Adhesion factors such as FimA, are required for contact and colonisation of host surfaces and plaque biofilms. A number of secreted proteases perform virulence functions: to mature fimbriae adhesions for cell-specific adhesion; to cleave host fibronectin and collagen for nutrient tissue infiltration; and to inactivate host cytokines and compliment factors and disrupt polymorphonuclear leukocytes, effectively inhibiting the local immune response. Expression of P. gingivalis adhesins and proteases, as well as the structure and therefore toxicity of its Lipid A molecule, are all induced in the presence of specific local conditions such as elevated temperature and hemin concentrations ^[4], ^[14], ^[18]. Therefore virulence is reduced in hosts supporting unfavourable conditions.

However the presence of P. gingivalis is not sufficient for formation of periodontal disease. A recent study demonstrated low abundance of P. gingivalis caused bone loss in mice with commensal oral microbiota, and not in germ-free mice ^[19]. It has been suggested that symbiosis between the three oral pathogenic bacteria P. gingivalis, Tannerella forsythia, and Treponema denticola - named the ‘red complex’ – has a unique role in the establishment of periodontal disease ^[20]. However, the more recent suggestion is that P. gingivalis initiates periodontal disease by mediating a shift in the homeostasis of the commensal oral microbiome towards dysbiosis, via alteration of the host immune response. For this reason P. gingivalis has been referred to as a ‘keystone pathogen’ ^[18].

Application to biotechnology

Concurrent to research examining the pathogenicity of P. gingivalis, is that focusing on development of novel treatments. In this aim, several avenues are being explored, including:

recombinant vaccination inducing immune response against the protease gingipains ^[21];
local inhibition of the host compliment system component C3 to reduce the sustained inflammation that supports P. gingivalis infection ^[22];
inhibition of protease gingipains by the proteins KYT -1 and KYT-36 from rice protein extracts ^[23];
compounds that block entry of P. gingivalis into oral epithelial cells ^[24];
altering the oral environment to make inhospitable to P. gingivalis ^[25], including by probiotic means ^[26].

Current research

A case of brain abscess by P. gingivalis in a patient with persistent periodontal disease was recently reported for the first time. The reporters suggest that P. gingivalis may be underestimated in its prevalence in brain abscesses of patients with poor dental hygiene ^[27].

Recent studies have associated P. gingivalis infection with esophageal cancer. Researchers found significantly higher levels of compounds unique to P. gingivalis in cancerous tissue compared with surrounding or normal tissue. This may be due to the preferential colonisation of cancerous tissue by this pathogen, or may implicate it in the development of esophageal cancer ^[28].