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Matthew Travers, Bench B, 43932863, 17/09/16 [1]

Porphyromonas gingivalis


Higher order taxa

Bacteria (Kingdom); Fibrobactere-Chlorobi-Bacteroidetes superphylum group (Domain); Bacteroidetes (Phylum); Bacteroidetes (Class); Bacteroidales (Order); Porphyromonadaceae (Family); Porphyromonas (Genus) [5]


Porphyromonas gingivalis
Type Strain: strain W83 [5]

Description and significance

Porphyromonas gingivalis are non-motile, gram negative, rod shaped bacteria typically found in subgingival plaque of those with periodontal disease [1]. The bacterium has also been found in other niches around the body including the GI tract, respiratory system and the colon [2]. Optimally the bacterium is cultured at 37˚C, forming black colonies on agar due to absorption of heme [3]. P. gingivalis found in the mouth is usually commensal, however can form complex biofilms with other bacteria to cause periodontitis [1]. Periodontitis typically causes inflammation of the gingival tissue, but can progress to cause stripping of supporting structures of the oral cavity. The disease has global implications, affecting countries even with easy access to medical care. The CDC found that 50% of US adults have some form of periodontal disease [4]. Thus P. gingivalis is imperative to study, to potentially restrict the number of periodontitis patients worldwide.

Genome structure

The genome of Porphyromonas gingivalis strain W83 is 2,343KB long with a GC composition of roughly 48.3% [5]. There are 1,990 identified ORFs, within which 463 essential genes have been identified. The circular genome is also comprised of two RNA and 53 tRNA genes capable of encoding 20 amino acids [6]. The genome also contains four ribosomal operons. 6% of the genome has been shown to contain transposable elements and other repetitive elements such as CRISPRs (clustered regularly interspaced short palindromic repeats). Several genes can be used to isolate oral cavity bacteria. Genes Rgp and Kgp are responsible for encoding the gingipain proteases distinctly found in Porphyromonas gingivalis , and can therefore be used to identify the bacterium from other species [7].

Cell structure and metabolism

The cell wall of Porphyromonas gingivalis is gram negative and comprised of lysine-rich layers of peptidoglycan [2]. P. gingivalis has no siderophores, instead relying on outer membrane receptor proteases and lipoproteins to acquire heme/iron [1]. Thus the metabolic requirements of the bacterium are centred around the acquisition of iron, and cells lacking iron display limited growth and virulence. The black colour of the colonised bacteria is also attributable to the acquisition of iron [8]. Porphyromonas gingivalis has been shown to form biofilms within the oral cavity. Its growth has been demonstrated to change depending on the presence of other bacteria within biofilms. Streptococcus cristatus CC5A has been shown to interfere with the fimA gene, which restricts the fimbriae and therefore adherence [9]. Furthermore F. nucleatum has been shown to result in the aggregation of P. gingivalis . Moreover, the interaction between P. gingivalis and S. gordonii results in 30 different genes between the species being differently regulated [10]. Due to biofilm formation P. gingivalis often exhibits abnormal expression of metabolic genes. This is attributed to T. denticola interactions, through which 34 metabolic genes involving Glycine and Thiamine pathways are differently regulated [11]. P. gingivalis glycine production is stimulated by co-culturing with T. denticola, due to the upregulation of two protease genes (PG0753 and PG0383). Furthermore, genes encoding both the synthesis and transport of Thiamine in P. gingivalis are transcribed at a higher rate [11]. Fatty acid biosynthesis genes fab5 and fab7 were all downregulated in co-culture experiments. Furthermore T. denticola has been shown to utilise free glycine and thiamine, contributing to pathogenesis of the biofilm and periodontitis [3].


P. gingivalis is an obligate anaerobe, generally found in the oral cavity. It survives primarily in subgingival plaque of those with periodontal disease, but colonises other environments including the upper GI and respiratory tract [12]. P. gingivalis is considered a part of the normal indigenous oral flora, but as an opportunistic pathogen it begins to cause periodontitis if the biofilm is not successfully removed. P. gingivalis is considered a secondary colonizer in plaque formation, as it adheres to primary colonisers [13]. Secondary colonisers are comprised of gram negative oral pathogens, such as P. gingivalis [14]. The shift from primary to secondary colonisers is caused by a change in the host immune system. As the biofilm accumulates below the gums, it shifts in composition from a primarily streptococcal to an actinomyces dominant microenvironment [15]. The immune system exhibits a neutrophilic mediated response which inflames soft tissue above the bone, commonly referred to as gingivitis [15]. The progression to periodontitis is caused by the immune system altering its response to the accumulation of the biofilm, using a lymphocytic and plasma cell mediated response [16]. This leads to redness, swelling and a tendency to bleed. This modifies the microenvironment once more, altering the composition of the biofilm to consist primarily of gram negative pathogens.


Several virulence factors contribute to the pathogenesis of P. gingivalis .


Rgp and Kgp genes have several functions within the bacteria. Along with some metabolic functions, adhesion and invasion are facilitated by these genes [17]. Kgp can bind to matrix proteins such as fibrinogen and fibronectin, facilitating colonisation of the matrix. The gingipains also facilitate the processing of precursor proteins of the fimbriae [17]. Furthermore, the gingipains of P. gingivalis have shown to increase the structural rigidity of biofilms. Gingipains have the ability to restrict host immune functions. Gingipains can cleave unique lysine residues in IgG1 and IgG3 antibodies, via lysine residues that are more accessible in these subclasses of the IgG antibody [18]. This can significantly restrict the classical complement system which the IgG antibodies activate. Further inhibition of the immune system is achieved through degrading host cytokines to subvert the host response [19]. The gingipains have been shown to target both free cytokines, as well as inhibiting cytokine receptors on the host cells [20]. IL-2 cytokine accumulation in T-cells is inhibited, interfering with communication and proliferation of the lymphocytes. This enables the bacteria to circumvent the host adaptive immune response. This is again targeted through lysine residues on both the receptors and the free molecules. A pro-inflammatory response typical of periodontitis is also induced by gingipains through activation of the p38α MAPK signal transduction pathway [21]. This transduction pathway upregulates the production of chemokines associated with inflammation, namely IL-8 and TNF-α [22]. The IL-8 expression has a plethora of effects invoking the stimulation of other cytokines within other immune cells such as leukocytes, monocytes and macrophages [23]. Furthermore, the increased IL-8 expression causes the differentiation of hematopoietic precursors of monocytes to osteoclasts, inducing the degradation of collagen/bone typical of periodontitis [23].


P. gingivalis fimbriae can be divided into three subgroups; short, long and accessory. The fimbriae are important for adhesion, invasion and colonisation. Long fimbriae, encoded by FimA, assist in the initial attachment of the bacteria [24]. Long fimbriae help form the biofilm through acting as an adhesin. Initial adhesion of P. gingivalis occurs between long fimbriae and the streptococcal centred biofilm through the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) receptor [25]. Long fimbriae have also been shown to adhere to human epithelial cells through the same region [1]. Short fimbriae are encoded by the Mfa1, and have a distinct role from long fimbriae. Short fimbriae facilitate cell-cell adhesion with other bacteria. Attachment is mediated through adhesin-receptor interactions via the SspA and SspB surface receptors on streptococcal bacteria [26]. The biofilm that forms following the short fimbriae attachment is comprised primarily of P. gingivalis and S. gordonii. Following the formation of the biofilm the Mfa1 gene is downregulated, most likely to alter the adhesin requirements of P. gingivalis as the streptococcal base is unavailable when the biofilm composition switches to predominantly gram negative anaerobes [25]. This phenotypic alteration of P. gingivalis combined with signalling molecules promotes recruitment of planktonic bacterial cells [26]. The key distinction between long and short fimbriae is that long fimbriae promote biofilm formation, while short fimbriae regulate biofilm development. Accessory proteins encoded downstream of the FimA gene (FimC, FimD and FimE) comprise less than 1% of expressed fimbriae content, but have a disproportionate effect on virulence [1]. Research has shown strains containing intact FimA genes have dramatically less virulence when lacking the three accessory proteins [25]. The fimbriae effect bacterial binding with matrix proteins and have an effect on CXC-chemokine receptors [25].

Lipopolysaccharide (LPS)

The LPS layer in P. gingivalis causes some of the inflammatory response seen in periodontitis. The LPS secreted by P. gingivalis contains a plethora of lipid A varieties [28]. Like other gram negative bacteria, the LPS signal of P. gingivalis is transported via the TLR4 transmembrane receptors to intracellular components. Unlike most gram negative varieties P. gingivalis can utilise a secondary pathway, usually utilised by gram positive bacteria, TLR2 [29]. This in turn stimulates the production of cytokines in through the TLR2-JNK pathway in THP-1 cells. Along with other virulence factors, LPS further produces the inflammation of periodontitis.

Polysaccharide Capsule

Encapsulated strains of Porphyromonas gingivalis display increased virulence in comparison to those without. The capsule is comprised of polysaccharides and involved in restriction of host immune responses [2]. The capsule downregulates the production of cytokines by immune cells. Encapsulated cells have also shown decreased levels of SOCS1 and SOCS3 cytokine signalling suppressors, increasing the proinflammatory ability of Porphyromonas gingivalis [27]. This causes reduced macrophage response, enabling the bacteria to avoid phagocytosis. Furthermore, the bacteria expressing capsules are internalised less often by dendritic cells or macrophages [3]. Moreover, encapsulated bacteria display higher resistance to phagocytosis than nonencapsulated bacteria taken up through macrophages [27].

Non-oral cavity infections

In certain patients, P. gingivalis displays pathogenesis outside of the oral microbiome. One condition associated with the presence of P. gingivalis is Rheumatoid arthritis [30]. This condition occurs due to the production of autoantibodies against citrullinated proteins (characterised by modified arginine residues). P. gingivalis has been shown to express PPAD, which are capable of modifying the arginine residues of host molecules in a way the host cannot [30]. This generates immune responses at the site of infection, followed by potential spread of the proteins to joints causing inflammation. Further infections associated with P. gingivalis include bacterial vaginosis and disruption of the liver [31].

Application to biotechnology

Biotechnological research has been focussed on the prevention and treatment of P. gingivalis infections. Vaccine targets have been isolated throughout the genome, with the most likely antigen candidates being RgpA and RgpB [32] [33]. Mouse models injected through Gene Gun techniques with rpgA showed increased antibodies in serum as well as decreased activity of the Rgp genes [34]. Further research has demonstrated that the bacterial fimbriae are useful vaccine targets because of their accessibility. The fimbriae are best utilised in an acellular vaccine as an immunomodulating adjuvant instead of a single antigen target [35]. Another aspect of vaccination against P. gingivalis is the benefits for rheumatoid arthritis patients. The PPAD gene resulting in the citrullinated proteins could be targeted as it is located on the cellular surface [30]. These targets for vaccines have the ability to alleviate the inflammatory response associated with both rheumatoid arthritis and periodontitis. Novel treatment methods are also being examined as therapeutic agents for the oral cavity. Manuka honey has been shown to act as an antibacterial against oral cavity P. gingivalis strains. The effect, caused by methylglyoxal, is able to reduce planktonic P. gingivalis populations but has shown limited effects on bacteria contained within biofilms [36]. In addition to its antibacterial capacity, honey has also displayed immunomodulatory effects capable of stimulating inflammatory cytokines [36].

Current research

Current research involved with P. gingivalis is focussed around establishing the oral microbiome as well as treatment methods that don’t involve vaccination. The prevention of oral cavity periodontitis is easily achieved through mechanical removal of the biofilm (brushing). Therefore, it is more economically viable to treat the condition. The primary focus of biofilm research is the relationships between the bacteria causing periodontitis [2]. P. gingivalis has been shown to alter genes of other bacteria in the biofilm. Current research is investigating the gene expression levels of different bacteria when in the presence of P. gingivalis [4]. Current research is also focussed on exploring non-oral cavity related infections caused by P. gingivalis . Rheumatoid arthritis and bacterial vaginosis are another two conditions epidemiologically linked to P. gingivalis for which treatments and preventative measures are being explored [30].


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4. CDC. (2015)

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6. Choi, CH., DeGuzman, JV., Lamont, RJ., Yilmaz, Ö. (2011) Genetic Transformation of an Obligate Anaerobe, P. gingivalis for FMN-Green Fluorescent Protein Expression in Studying Host-Microbe Interaction. J Clin Periodontol6.

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11. Tan, KH., Seers, CA., Dashper, SG., Mitchell, HL., Pyke, JS., Meuric, V., Slakeski, N., Cleal, SM., Chambers, JL., McConville, MJ., Reynolds, EC. (2014) Short Fimbriae of Porphyromonas gingivalis and Their Role in Coadhesion with Streptococcus gordonii. PLoS Pathog 10: e1003955.

12. Griffen, AL., Becker, MR., Lyons, SR., Moeschberger, ML., Leys, EJ. (1998) Prevalence of Porphyromonas gingivalis and Periodontal Health Status. J Clin Microbiol 36:3239-3242.

13. Yamaguchi, M., Noiri, Y., Kuboniwa, M., Yamamoto, R., Asahi, Y., Maezono, H., Hayashi, M., Ebisu, S. (2013) Porphyromonas gingivalis biofilms persist after chlorhexidine treatment. European Journal of Oral Sciences 121:162-168.

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15. Hajishengallis, G., Liang, S., Payne, MA., Hashim, A., Jotwani, R., Eskan, MA., McIntosh, ML., Alsam, A., Kirkwood, KL., Lambris, JD., Darveau, RP., Curtis, MA. (2011) A Low-Abundance Biofilm Species Orchestrates Inflammatory Periodontal Disease through the Commensal Microbiota and the Complement Pathway. Cell Host Microbe. 10:497-506.

16. Shah, HN., Gharbia, SE. (1993) Studies on the physiology and ecology of black-pigmented Gram-negative anaerobes which may be important in disease development. Medical Microbiology 6165-172.

17. Chen, T., Nakayama, K., Belliveau, L., Duncan, MJ. (2001) Porphyromonas gingivalis Gingipains and Adhesion to Epithelial Cells. Infect Immun 693048-3056.

18. Vincents, B., Guentsch, A., Kostolowska, D., von Pawel-Rammingen, U., Eick, S., Potempa, J., Abrahamson, M. (2011) Cleavage of IgG(1) and IgG(3) by gingipain K from Porphyromonas gingivalis may compromise host defense in progressive periodontitis. Faseb j 253741-3750.

19. Yamatake, K., Maeda, M., Kadowaki, T., Takii, R., Tsukuba, T., Ueno, T., Kominami, E., Yokota, S., Yamamoto, K. (2007) Role for Gingipains in Porphyromonas gingivalis Traffic to Phagolysosomes and Survival in Human Aortic Endothelial Cells. Infect Immun 75:2090-2100.

20. Mężyk-Kopeć, R., Bzowska, M., Potempa, J., Bzowska, M., Jura, N., Sroka, A., Black, RA., Bereta, J. (2005) Inactivation of Membrane Tumor Necrosis Factor Alpha by Gingipains from Porphyromonas gingivalis . Infect Immun 73:1506-1514.

21. Patil, CS., Kirkwood, KL. (2014) p38 MAPK Signaling in Oral-related Diseases. Journal of Dental Research 86:812-825.

22. Zhang, D., Chen, L., Li, S., Gu, Z., Yan, J. (2008) Lipopolysaccharide (LPS) of Porphyromonas gingivalis induces IL-1β, TNF-α and IL-6 production by THP-1 cells in a way different from that of Escherichia coli LPS. Innate Immunity 14:99-107.

23. Grenier, D., Tanabe, S. (2010) Porphyromonas gingivalis Gingipains Trigger a Proinflammatory Response in Human Monocyte-derived Macrophages Through the p38α Mitogen-activated Protein Kinase Signal Transduction Pathway. Toxins (Basel)2:341-352.

24. Furuta, N., Takeuchi, H., Amano, A. (2009) Entry of Porphyromonas gingivalis Outer Membrane Vesicles into Epithelial Cells Causes Cellular Functional Impairment. Infect Immun 77:4761-4770.

25. Pierce, DL., Nishiyama, S., Liang, S., Wang, M., Triantafilou, M., Triantafilou, K., Yoshimura, F., Demuth, DR., Hajishengallis, G. (2009) Host Adhesive Activities and Virulence of Novel Fimbrial Proteins of Porphyromonas gingivalis . Infect Immun 77:3294-3301.

26. Grenier, D. (2013) Porphyromonas gingivalis Outer Membrane Vesicles Mediate Coaggregation and Piggybacking of Treponema denticola and Lachnoanaerobaculum saburreum. International Journal of Dentistry 2013:4.

27. Singh, A., Wyant, T., Anaya-Bergman, C., Aduse-Opoku, J., Brunner, J., Laine, ML., Curtis, MA., Lewis, JP. (2011) The Capsule of Porphyromonas gingivalis Leads to a Reduction in the Host Inflammatory Response, Evasion of Phagocytosis, and Increase in Virulence. Infect Immun 79:4533-4542.

28. Darveau, RP., Pham, TTT., Lemley, K., Reife, RA., Bainbridge, BW., Coats, SR., Howald, WN., Way, SS., Hajjar, AM. (2004) Porphyromonas gingivalis Lipopolysaccharide Contains Multiple Lipid A Species That Functionally Interact with Both Toll-Like Receptors 2 and 4. Infect Immun72:5041-5051.

29. Burns, E., Eliyahu, T., Uematsu, S., Akira, S., Nussbaum, G. (2010) TLR2-Dependent Inflammatory Response to Porphyromonas gingivalis Is MyD88 Independent, whereas MyD88 Is Required To Clear Infection. The Journal of Immunology 184:1455-1462.

30. Mikuls, TR., Payne, JB., Yu, F., Thiele, GM., Reynolds, RJ., Cannon, GW., Markt, J., McGowan, D., Kerr, GS., Redman, RS., Reimold, A., Griffiths, G., Beatty, M., Gonzalez, S., Bergman, DA., Hamilton, BC., Erickson, AR., Sokolove, J., Robinson, W., Walker, C., Chandad, F., O’Dell, JR. (2014) Periodontitis and Porphyromonas gingivalis in Patients with Rheumatoid Arthritis. Arthritis Rheumatol66:1090-1100.

31. Ishikawa, M., Yoshida, K., Okamura, H., Ochiai, K., Takamura, H., Fujiwara, N., Ozaki, K. (2013) Oral Porphyromonas gingivalis translocates to the liver and regulates hepatic glycogen synthesis through the Akt/GSK-3β signaling pathway. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease1832:2035-2043.

32. Gonzalez, D., Tzianabos, AO., Genco, CA., Gibson, IF. (2003) Immunization with Porphyromonas gingivalis Capsular Polysaccharide Prevents P. gingivalis -Elicited Oral Bone Loss in a Murine Model. Infect Immun 71:2283-2287.

33. Curtis, MA., Aduse Opoku, J., Rangarajan, M., Gallagher, A., Sterne, JAC., Reid, CR., Evans, HEA., Samuelsson, B. (2002) Attenuation of the Virulence of Porphyromonas gingivalis by Using a Specific Synthetic Kgp Protease Inhibitor. Infect Immun 70:6968-6975.

34. Vishakha G, Anoop K, Ranjan M, Gagandeep K. (2014) Porphyromonas gingivalis Antigenic Determinants - Potential Targets for the Vaccine Development against Periodontitis. Infectious Disorders - Drug Targets14:1-13.

35. Reynolds, EC., O'Brien-Simpson, N., Rowe, T., Nash, A., McCluskey, J., Vingadassalom, D., Kleanthous, H. (2015) Prospects for treatment of Porphyromonas gingivalis -mediated disease – immune-based therapy. J Oral Microbiol Research7.

36. Eick, S., Schäfer, G., Kwieciński, J., Atrott, J., Henle, T., Pfister, W. (2014) Honey – a potential agent against Porphyromonas gingivalis : an in vitro study. BMC Oral Health 14:1-9.

  1. micr3004

This page is written by Matthew Travers for the MICR3004 course, Semester 2, 2016